The habenula is a small and bilateral nucleus above dorsal thalamus, which contains several different types of neurons. The habenula has extensive connections with the forebrain, septum and monoaminergic nuclei in the midbrain and brainstem. Habenula is known as an 'anti-reward' nucleus, which can be activated by aversive stimulus and negative reward prediction errors. Accumulating researchs have implicated that the habenula is involved in several behaviors crucial to survival. Meanwhile, the roles of the habenula in neuropsychiatric diseases have received increasing attention. This review summaries the studies regarding the roles of habenula and the related circuits in neuropathic pain, depression, drug addiction and schizophrenia, and discusses the possibility to use the habenula as a treatment target.
Depressive Disorder ; Habenula ; Humans ; Mental Disorders ; pathology ; Mesencephalon ; Neurons ; metabolism ; Reward

Neuroprotective effect of scorpion venom on Parkinson's disease (PD) has already been reported. The present study was aimed to investigate whether scorpion venom heat resistant peptide (SVHRP) could attenuate ultrastructural abnormalities in mitochondria and oxidative stress in midbrain neurons of early-stage PD model. The early-stage PD model was established by injecting 6-hydroxydopamine (6-OHDA) (20 μg/3 μL normal saline with 0.1% ascorbic acid) into the striatum of Sprague Dawley (SD) rats unilaterally. The rats were intraperitoneally administered with SVHRP (0.05 mg/kg per day) or vehicle (saline) for 1 week. Two weeks after 6-OHDA treatment, the rats received behavior tests for validation of model. Three weeks after 6-OHDA injection, the immunoreactivity of dopaminergic neurons were detected by immunohistochemistry staining, and the ultrastructure of neuronal mitochondria in midbrain was observed by electron microscope. In the meantime, the activities of monoamine oxidase-B (MAO-B), superoxide dismutase (SOD) and content of malondialdehyde (MDA) in the mitochondria of the midbrain neurons, as well as the inhibitory ability of hydroxyl free radical and the antioxidant ability in the serum, were measured by corresponding kits. The results showed that 6-OHDA reduced the optical density of dopaminergic neurons, induced damage of mitochondrial ultrastructure of midbrain neurons, decreased SOD activity, increased MAO-B activity and MDA content, and reduced the antioxidant ability of the serum. SVHRP significantly reversed the previous harmful effects of 6-OHDA in early-stage PD model. These findings indicate that SVHRP may contribute to neuroprotection by preventing biochemical and ultrastructure damage changes which occur during early-stage PD.
Animals ; Antioxidants ; metabolism ; Corpus Striatum ; Disease Models, Animal ; Dopaminergic Neurons ; drug effects ; Malondialdehyde ; metabolism ; Mesencephalon ; cytology ; Mitochondria ; metabolism ; ultrastructure ; Neuroprotective Agents ; pharmacology ; Oxidative Stress ; Oxidopamine ; Parkinson Disease ; drug therapy ; Peptides ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Scorpion Venoms ; pharmacology ; Superoxide Dismutase ; metabolism

OBJECTIVE: To observe the protein expression of growth associated protein-43 (GAP-43) in midbrain ventral tegmental area in morphine withdrawal rats at different time, and to evaluate the effect of GAP-43 on morphine withdrawal memory. METHODS: Rat models of morphine dependent 1 week, 2 weeks and 4 weeks were established by morphine hydrochloride intraperitoneal injection with increasing doses to establish natural withdrawal. The protein expression of GAP-43 in midbrain ventral tegmental area was observed by immunohistochemical staining and the results were analyzed by Image-Pro Plus 5.1 image analysis system. RESULTS: With prolongation of dependent time, the expression of GAP-43 was decreased then increased in midbrain ventral tegmental area. CONCLUSION GAP-43 could play a role in morphine withdrawal memory in midbrain ventral tegmental area.
Animals ; Behavior, Animal/drug effects* ; Disease Models, Animal ; Female ; GAP-43 Protein/metabolism* ; Immunohistochemistry ; Male ; Mesencephalon/metabolism* ; Morphine/adverse effects* ; Morphine Dependence/metabolism* ; Naloxone/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Substance Withdrawal Syndrome/metabolism* ; Time Factors ; Ventral Tegmental Area/metabolism*

OBJECTIVETo identify the protective effect of lipopolysaccharide (LPS) preconditioning against LPS-induced inflammatory damage in dopaminergic neurons of midbrain slice culture and the possible mechanisms.

METHODSAfter cultured in vitro for 14 d, the rat organotypic midbrain slices were pretreated with different concentrations (0, 1, 3, 6 or 10 ng/mL) of LPS for 24 h followed by treatment with 100 ng/mL LPS for 72 h. The whole slice viability was determined by measurement of the activity of lactic acid dehydrogenase (LDH). Tyrosine hydroxylase-immunoreactive (TH-IR) neurons and CD11b/c equivalent-immunoreactive (OX-42-IR) microglia in the slices were observed by immunohistochemical method, and tumor necrosis factor-alpha (TNF-alpha) levels in the culture media were detected by enzyme-linked immunosorbent assays (ELISA).

RESULTSIn the slices treated with 100 ng/mL LPS for 72 h, the number of TH-IR neurons reduced from 191+/-12 in the control slices to 46+/-4, and the LDH activity elevated obviously (P < 0.01), along with remarkably increased number of OX-42-IR cells and production of TNF-alpha (P < 0.01). Preconditioning with 3 or 6 ng/mL LPS attenuated neuron loss (the number of TH-IR neurons increased to 126+/-12 and 180+/-13, respectively) and markedly reduced LDH levels (P < 0.05), accompanied by significant decreases of OX-42-IR microglia activation and TNF-alpha production (P < 0.05).

CONCLUSIONLow-dose LPS preconditioning could protect dopaminergic neurons against inflammatory damage in rat midbrain slice culture, and inhibition of microglial activation and reduction of the proinflammatory factor TNF-alpha production may contribute to this protective effect. Further understanding the underlying mechanism of LPS preconditioning may open a new window for treatment of Parkinson's disease.

Animals ; CD11 Antigens ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Immunohistochemistry ; Inflammation ; chemically induced ; pathology ; L-Lactate Dehydrogenase ; metabolism ; Lipopolysaccharides ; administration & dosage ; toxicity ; Mesencephalon ; drug effects ; immunology ; pathology ; Microglia ; drug effects ; immunology ; pathology ; Nerve Degeneration ; metabolism ; pathology ; prevention & control ; Neurons ; drug effects ; immunology ; pathology ; Organ Culture Techniques ; Rats ; Tumor Necrosis Factor-alpha ; metabolism ; Tyrosine 3-Monooxygenase ; metabolism

The present study was undertaken to investigate the effect of melatonin on the content of β-endorphin (β-EP) in the hypothalamic arcuate nucleus (Arc) and periaqueductal grey (PAG) of midbrain in morphine withdrawal mice. Male Kunming mice were injected subcutaneously (s.c.) with an increasing dose of morphine continuously for 8 d to establish morphine dependence model. Withdrawal response was induced by naloxone (3 mg/kg body weight, s.c.). The potency of withdrawal response was evaluated according to the jumping times and body weight loss. Ninty minutes prior to the precipitation of naloxone, 80 mg/kg body weight of melatonin (MEL) was injected intraperitoneally (i.p.) to observe its antagonistic effect on the withdrawal response in morphine-dependent mice. After behavioral observation, radioimmunoassay was used to determine the content of β-EP in the PAG of midbrain, and immunohistochemical assay was used to observe the intensity of β-EP-like immunoreactivity in the Arc in mice. It was shown that MEL inhibited the naloxone-precipitated withdrawal responses in mice significantly (P<0.05). In the meantime, MEL increased the content of β-EP in the PAG of midbrain significantly (P<0.05) and attenuated the intensity of β-EP-like immunoreactivity in the Arc in mice (P<0.05). The results suggest that MEL increases the content of β-EP in the PAG of midbrain, decrease the content of β-EP in the Arc in morphine withdrawal mice.
Animals ; Arcuate Nucleus of Hypothalamus ; drug effects ; metabolism ; Male ; Melatonin ; pharmacology ; Mesencephalon ; drug effects ; metabolism ; Mice ; Morphine Dependence ; Naloxone ; Periaqueductal Gray ; drug effects ; metabolism ; Substance Withdrawal Syndrome ; beta-Endorphin ; metabolism

PURPOSE: Gender differences in personality are considered to have biological bases. In an attempt to understand the gender differences of personality on neurobiological bases, we conducted correlation analyses between regional brain glucose metabolism and temperament factors of personality in males and females. MATERIALS AND METHODS: Thirty-six healthy right-handed volunteers (18 males, 33.8+/-17.6 y; 18 females, 36.2+/-20.4 y) underwent FDG PET at resting state. Three temperament factors of personality (novelty seeking (NS), harm avoidance (HA), reward dependence (RD)) were assessed using Cloninger's 240-item Temperament and Character Inventory (TCI) within 10 days of FDG PET scan. Correlation between regional glucose metabolism and each temperament factor was tested using SPM2. RESULTS: In males, a significant negative correlation between NS score and glucose metabolism was observed in the bilateral superior temporal gyri, the hippocampus and the insula, while it was found in the bilateral middle frontal gyri, the right superior temporal gyrus and the left cingulate cortex and the putamen in females. A positive HA correlation was found in the right midbrain and the left cingulate gyrus in males, but in the bilateral basal ganglia in females. A negative RD correlation was observed in the right middle frontal and the left middle temporal gyri in males, while the correlation was found in the bilateral middle frontal gyri and the right basal ganglia and the superior temporal gyrus in females. CONCLUSION: These data demonstrate different cortical and subcortical metabolic correlates of temperament factors of personality between males and females. These results may help understand biological substrate of gender differences in personality and susceptibility to neuropsychiatric illnesses.
Basal Ganglia ; Brain ; Female ; Glucose ; Gyrus Cinguli ; Hippocampus ; Humans ; Male ; Mesencephalon ; Metabolism ; Positron-Emission Tomography ; Putamen ; Reward ; Temperament* ; Volunteers

PURPOSE: Gender differences in personality are considered to have biological bases. In an attempt to understand the gender differences of personality on neurobiological bases, we conducted correlation analyses between regional brain glucose metabolism and temperament factors of personality in males and females. MATERIALS AND METHODS: Thirty-six healthy right-handed volunteers (18 males, 33.8+/-17.6 y; 18 females, 36.2+/-20.4 y) underwent FDG PET at resting state. Three temperament factors of personality (novelty seeking (NS), harm avoidance (HA), reward dependence (RD)) were assessed using Cloninger's 240-item Temperament and Character Inventory (TCI) within 10 days of FDG PET scan. Correlation between regional glucose metabolism and each temperament factor was tested using SPM2. RESULTS: In males, a significant negative correlation between NS score and glucose metabolism was observed in the bilateral superior temporal gyri, the hippocampus and the insula, while it was found in the bilateral middle frontal gyri, the right superior temporal gyrus and the left cingulate cortex and the putamen in females. A positive HA correlation was found in the right midbrain and the left cingulate gyrus in males, but in the bilateral basal ganglia in females. A negative RD correlation was observed in the right middle frontal and the left middle temporal gyri in males, while the correlation was found in the bilateral middle frontal gyri and the right basal ganglia and the superior temporal gyrus in females. CONCLUSION: These data demonstrate different cortical and subcortical metabolic correlates of temperament factors of personality between males and females. These results may help understand biological substrate of gender differences in personality and susceptibility to neuropsychiatric illnesses.
Basal Ganglia ; Brain ; Female ; Glucose ; Gyrus Cinguli ; Hippocampus ; Humans ; Male ; Mesencephalon ; Metabolism ; Positron-Emission Tomography ; Putamen ; Reward ; Temperament* ; Volunteers

The effect of systemic administration of nonspecific nitric oxide synthase inhibitor (N(omega)-nitro-L-arginine methyl ester, L-NAME) on morphine analgesia tolerance was observed by using the thermal tail-flick method, and the roles of NO and NMDA receptors in morphine analgesia tolerance were evaluated on the basis of the expressions of nNOS mRNA, NR1A mRNA and NR2A mRNA in spinal cord and midbrain. Thirty-six healthy adult Sprague-Dawley rats were randomly divided into six groups (6 rats per group). Group 1, control group, received a subcutaneous (s.c.) injection of normal saline (1 ml); Groups 2, 3, 4, 5 and 6, the treatment groups received s.c. injection of L-NAME 10 mg/kg, L-NAME 20 mg/kg, morphine 10 mg/kg, L-NAME 10 mg/kg + morphine 10 mg/kg, and L-NAME 20 mg/kg + morphine 10 mg/kg, respectively. All rats received s.c. injections twice per day (8:00 and 17:00). The tail-flick latency (TFL) was measured in each rat before the injection as a baseline value, and then TFL at 50 min after the 1st injection every day as the measuring values. The animals (except for groups 2 and 5) were decapitated at 80 min after the last injection on the 8th day. The spinal segments and midbrain were removed for analysis of nNOS mRNA, NR1A mRNA and NR2A mRNA expressions by the RT-PCR method. The results showed that TFL remained unchangeable in group 2 compared with baseline value during the 7-day observation, while increased significantly on the 7th day in group 3. In group 4, TFL was longest on the 1st day, then decreased gradually from the 2nd day to the 6th day, and restored to the baseline value on the 6th day. In group 5, TFL showed a decreasing tendency during the 7-day observation, but was still significantly longer than the baseline value on the 7th day. The changes of TFL obtained in group 6 were similar to those in group 5. The results of RT-PCR showed that as compared with group 1, nNOS mRNA expressions in spinal cord and midbrain were significantly down-regulated in group 3, but the expressions of the NR1A mRNA and NR2A mRNA in both groups were similar, while the nNOS mRNA, NR(1A) mRNA and NR(2A) mRNA expressions were all significantly up-regulated in group 4. As compared with group 4, the expressions of nNOS mRNA, NR(1A) mRNA and NR(2A) mRNA were significantly inhibited in group 6. These results suggest that the expressions of nNOS and NMDA receptors in spinal cord and midbrain were significantly up-regulated in the rats with morphine analgesia tolerance. Chronic co-administration of L-NAME could effectively inhibit the morphine-induced overexpressions of nNOS and NMDA receptors, and postpone the development of morphine analgesia tolerance. Based on the results of this study, it is concluded that NO/NMDA receptor in spinal cord and midbrain is closely related to the development of morphine analgesia tolerance.
Analgesia ; Animals ; Drug Tolerance ; Mesencephalon ; metabolism ; Morphine ; pharmacology ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide Synthase ; antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; metabolism ; Spinal Cord ; metabolism ; Up-Regulation

In the experiment, we designed and synthesized two siRNAs based on the sequence of nuclear receptor-related factor 1 (Nurr1) mRNA. They were separately subcloned into the plasmid of pSilenCircle (pSC) containing U6 promoter. The pSC-Nurr1 vectors (pSC-N1 and pSC-N2) specific to Nurr1 gene and the negative control vector of short-hairpin RNA (shRNA) eukaryotic expression vector were constructed. We cultured the dopaminergic cell line MN9D and the verified vectors were transfected with LipofectamineTM 2000 in vitro. The positive cell clones transfected with pSC were obtained after being screened with 500 mug/ml G418. After that, the silencing effects of Nurr1 and TH mRNA or protein were detected by real time RT-PCR and Western blot. The neurite extension of MN9D cells was observed and photographed by inverted microscope. The results showed that Nurr1 mRNA expression in MN9D cells was specifically down-regulated by the vectors of pSC-N1 and pSC-N2, and the silencing effects were 62.3% and 45.6%, respectively. The dopaminergic phenotype of TH mRNA was also suppressed significantly and the silencing effects were 76.3% and 62.6%, respectively. Meanwhile, the expressions of Nurr1 and TH proteins were also significantly suppressed, and the silencing effects of Nurr1 and TH protein were 57.4%, 72.0% and 79.1%, 70.1% respectively. The negative control and liposome groups had no effect on the two genes. In conclusion, Nurr1 shRNA expressing vectors can inhibit the expressions of Nurr1 and TH mRNA or protein in MN9D cells, and Nurr1 might play a role in neurite extension of MN9D cells. Nurr1 shRNA expressing vector may provide a novel applicable strategy for the study on the function of the genes associated with Parkinson disease and the development of dopaminergic neuron.
Cell Line ; Dopaminergic Neurons ; cytology ; metabolism ; Down-Regulation ; Fetus ; Humans ; Mesencephalon ; cytology ; Neurites ; physiology ; Nuclear Receptor Subfamily 4, Group A, Member 2 ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; Transfection ; Tyrosine 3-Monooxygenase ; genetics ; metabolism

BACKGROUND: To investigate postoperative changes in the cerebral glucose metabolism of patients with mesial temporal lobe epilepsy (MTLE), statistical parametric mapping (SPM) analysis was performed on pre- and post-operative 18F-fluorodeoxy glucose positron emission tomographic (FDG-PET) images. METHODS: We included 28 patients with MTLE who had under-gone surgery and had been seizure free postoperatively (16 had left MTLE and 12 right MTLE). All patients showed hippocampal sclerosis by pathology or brain MRI. FDG-PET images of the 12 right TLE patients were reversed to lateralize the epileptogenic zone to the left side in all patients. RESULTS: Application of the paired t-test in SPM to pre- and postoperative FDG-PETs showed that the postoperative glucose metabolism decreased in the caudate nucleus, pulvinar of thalamus, fusiform gyrus, lingual gyrus, and in the posterior region of the insular cortex in the hemisphere ipsilateral to resection, whereas postoperative glucose metabolism increased in the anterior region of the insular cortex, temporal stem white matter, midbrain, inferior precentral gyrus, anterior cingulate gyrus, and supramarginal gyrus in the hemisphere ipsilateral to resection. No significant postsurgical changes of cerebral glucose metabolism occurred in the contralateral hemisphere. Subtraction between pre- and postoperative FDG-PET images in individual patients produced similar findings to the SPM results. CONCLUSION: This study suggests that brain regions showing a postoperative increase in glucose metabolism appear to represent the propagation pathways of ictal and interictal epileptic discharges in MTLE while a postoperative decrease in glucose metabolism may be related to a permanent loss of afferents from resected anterior-mesial temporal structures.
Anterior Temporal Lobectomy ; Brain ; Caudate Nucleus ; Electrons ; Epilepsy, Temporal Lobe* ; Glucose ; Gyrus Cinguli ; Humans ; Magnetic Resonance Imaging ; Mesencephalon ; Metabolism ; Pathology ; Pulvinar ; Sclerosis ; Seizures ; Temporal Lobe* ; Thalamus