Cordycepin exerts neuroprotective effects against excitotoxic neuronal death. However, its direct electrophysiological evidence in Alzheimer's disease (AD) remains unclear. This study aimed to explore the electrophysiological mechanisms underlying the protective effect of cordycepin against the excitotoxic neuronal insult in AD using whole-cell patch clamp techniques. β-Amyloid (Aβ) and ibotenic acid (IBO)-induced injury model in cultured hippocampal neurons was used for the purpose. The results revealed that cordycepin significantly delayed Aβ + IBO-induced excessive neuronal membrane depolarization. It increased the onset time/latency, extended the duration, and reduced the slope in both slow and rapid depolarization. Additionally, cordycepin reversed the neuronal hyperactivity in Aβ + IBO-induced evoked action potential (AP) firing, including increase in repetitive firing frequency, shortening of evoked AP latency, decrease in the amplitude of fast afterhyperpolarization, and increase in membrane depolarization. Further, the suppressive effect of cordycepin against Aβ + IBO-induced excessive neuronal membrane depolarization and neuronal hyperactivity was blocked by DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine A₁ receptor-specific blocker). Collectively, these results revealed the suppressive effect of cordycepin against the Aβ + IBO-induced excitotoxic neuronal insult by attenuating excessive neuronal activity and membrane depolarization, and the mechanism through the activation of A₁R is strongly recommended, thus highlighting the therapeutic potential of cordycepin in AD.
Action Potentials ; Adenosine ; Alzheimer Disease ; Fires ; Ibotenic Acid ; Membranes ; Neurons ; Neuroprotection ; Neuroprotective Agents ; Patch-Clamp Techniques ; Pyramidal Cells

Amanita pantherina and Amanita muscaria have been called hallucinogenic fungi. They contain ibotenic acid and muscimol. Patients may appear to be intoxicated or have apparent 'patherina-muscaria' syndrome, which is atropine-like, but fatality is rare. Confusion, dizziness, tiredness, visual and auditory hypersensitivity, space distortion, unawareness of time, dryness of the mouth, mydriasis and hallucination may occur. Also, in exceptionally rare severe poisoning cases, convulsion, coma and death may occur. A 50-year-old well-nourished and developed man was admitted to this hospital with a 30-minute history of semicoma and involuntary contraction of the extremities which had developed following mushroom ingestion 2 hours earlier. Ingested mushrooms were revealed to be A. pantherina by a mycologist. The patient recovered 7 hours later after only supportive management, but the next day he couldn't recalled any of his hospital duration from admission to 20 hours later. Only a few reports have precise descriptions of the subspecies of the genus and there was no reports on poisoning by A. pantherina in Korea. In addition, there are no reports of amnesia following poisoning by A. pantherina. For these reasons, we report this case, together with a review of the literature.
Agaricales ; Amanita* ; Amnesia* ; Coma ; Dizziness ; Eating ; Extremities ; Fungi ; Hallucinations ; Humans ; Hypersensitivity ; Ibotenic Acid ; Korea ; Middle Aged ; Mouth ; Muscimol ; Mushroom Poisoning ; Mydriasis ; Poisoning* ; Seizures

The present study was designed to elucidate the effects of rostral basal forebrain lesions on neuropeptide containing neurons in the cerebral cortex. Nine male Sprague-Dawley rats[250-300gm] received bilateral injections of ibotenic acid into the basal forebrain[A : +0.7mm, L : 2.3mm, D : 8.6mm] and additional five served as sham operated animals. Brains were removed at 8-14 days after lesioning and frozen coronal sections of 40 micrometer thickness were made. Immunohistochemical staining was performed against the somatostatin[SOM], neuropeptide Y[NPY], and vasoactive intestinal polypeptide[VIP]. No differences were observed in the number of the SOM-immunoreactive[SOM-ir] or NPY-ir neurons between the lesioned and the control groups. Density of the NPY-ir fibers also did not show any significant difference between the two groups. In contrast, the number of VIP-ir neurons in the frontal cortex was significantly reduced following the basal forebrain lesioning. These results suggest the functional relationship between the basal forebrain and the cortical VIP-ir neurons.
Animals ; Brain ; Cerebral Cortex* ; Humans ; Ibotenic Acid ; Immunohistochemistry ; Male ; Neurons* ; Neuropeptide Y ; Neuropeptides* ; Prosencephalon* ; Rats* ; Rats, Sprague-Dawley ; Somatostatin ; Vasoactive Intestinal Peptide

OBJECTIVETo assess the changes of neurobehavioral function in a neonatal mouse model of excitotoxic brain damage.

METHODSFifty-five 5-day-old ICR neonatal mice were randomly assigned to three groups: blank (no intravenous) control (n=20), saline control (n=20) and excitotoxic brain damage model (ibotenic acid treatment, n=15). Behavioral function was evaluated by the surface righting reflex test (postnatal days 6-10), the swimming test (postnatal days 8-12) and the Y-maze discrimination learning test (postnatal days 33-34).

RESULTSRighting time in the surface righting reflex test in the ibotenic acid treatment group on postnatal days 6-10 was more prolonged than that in the two control groups (p<0.05). Swimming test scores in the ibotenic acid treatment group were significantly lower than those in the two control groups (p<0.05). In the Y-maze discrimination learning test, the mice from the ibotenic acid treatment group performed significantly worse than two control groups, presenting with increased learning times (19.79+/-2.42 vs 16.29+/-2.48 or 16.30+/-2.37; p<0.05) and achieving a lower correct percentage (86.7% vs 96.5% or 95.0%) (p<0.05).

CONCLUSIONSThe developmental reflexes and learning and memory functions were impaired in neonatal mice following excitotoxic brain damage. Behavioral testing is useful in the evaluation of early developmental reflexes and long-term neurobehavioral outcome in neonatal mice with excitotoxic brain damage.

Animals ; Animals, Newborn ; Behavior, Animal ; drug effects ; Brain ; drug effects ; Excitatory Amino Acid Agonists ; toxicity ; Female ; Ibotenic Acid ; toxicity ; Male ; Maze Learning ; drug effects ; Mice ; Mice, Inbred ICR ; Swimming

OBJECTIVESome research has shown that learning and memory function impairments in rats with hypothyroidism are associated with triiodothyronine (T3) deficiency in neurons. This study aimed to investigate the effects of L-T3 administration on learning and memory behaviors in neonatal mice with excitotoxic brain damage.

METHODSSeventy-one 5-day-old ICR neonatal mice were randomly assigned to five groups: controls that received intracerebral and intraperitoneal injections of phosphate buffered saline (PBS) (n=14); a group that received intracerebral injections of ibotenic acid (IA) and intraperitoneal injection of PBS (n=14); 3 groups that received intracerebral injections of IA and intraperitoneal injection of L-T3 at 0.2, 0.5, and 1 microg/kg, respectively (n=14-15). Intraperitoneal injections were done 1, 24, 48, 72 and 96 hrs after intracerebral injections. Learning and memory functions were evaluated by the Y-maze discrimination learning test on postnatal days 33-34.

RESULTSThe learning and memory functions in the highest L-T3 dose group were significantly better than those in the IA, and the lower L-T3 dose groups, presenting with decreased number of trials to criterion[15.8 + or - 4.5 vs 21.3 + or - 6.3 (IA group), 20.5 + or - 6.0 (0.2 microg/kg L-T3 group) or 21.0 + or - 6.5 (0.5 microg/kg L-T3 group); P<0.05], and achieving a higher correct percentage [91.4+ or - 9.5% vs 79.3 + or - 10.0% (IA group), 77.9 + or - 14.2% (0.2 microg/kg L-T3 group) or 80.7 + or - 12.2% (0.5 microg/kg L-T3 group); P<0.05].

CONCLUSIONSHigh-dose L-T3 (1 microg/kg) may improve learning and memory functions in mice following excitotoxic brain damage.

Animals ; Animals, Newborn ; Brain ; drug effects ; Excitatory Amino Acid Agonists ; toxicity ; Female ; Ibotenic Acid ; toxicity ; Learning ; drug effects ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; Mice ; Mice, Inbred ICR ; Triiodothyronine ; pharmacology

OBJECTIVETo observe the protective effect of Panax notoginseng saponins (PNS) on the level of synaptophysin ptotein in brain in rat model with Alzheimer's disease (AD).

METHODThe AD rat models were established by intra-peritoneal injection of D-galactose combined with excitatory neurotoxin ibotenic acid injection into bilateral nbM. The activity and content of synaptophysin protein in brain were determined by immunohistochemistry analysis.

RESULTPNS could reduce the lesion of level of synaptophysin protein in brain, as compared with those of model group's rats.

CONCLUSIONPNS plays a protective role by reducing down of the level of synaptophysin protein in brain in lesion of AD animal model.

Alzheimer Disease ; chemically induced ; metabolism ; pathology ; Animals ; Basal Nucleus of Meynert ; drug effects ; pathology ; Brain ; metabolism ; pathology ; Galactose ; toxicity ; Ginsenosides ; isolation & purification ; pharmacology ; Ibotenic Acid ; toxicity ; Neuroprotective Agents ; isolation & purification ; pharmacology ; Panax ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar ; Synaptophysin ; metabolism

BACKGROUNDThe neonatal ventral hippocampal lesion (NVHL) rat model has been proposed as an experimental model for schizophrenia. NVHL rats display impaired central nervous system (CNS) inhibition, which may lead to a phenomenon similar to P50 sensory gating deficits observed in schizophrenic patients. In this study, we investigated whether sensory gating deficits occurred in the NVHL rat as a model for schizophrenia.

METHODSWe created the NVHL rat model using ibotenate. The P20 and N40 were measured to assess sensory response and gating in NVHL and sham rats. Epidural electrodes recorded evoked potentials (EPs), from which latencies, amplitudes, difference scores (S1-S2), and gating ratios (S2/S1) were assessed.

RESULTSCompared with sham controls, prolonged S1 N40 latency and decreased S2 N40 amplitude were detected in the NVHL group. In neither difference scores nor gating ratios, a significant difference was found between NVHL group and sham controls.

CONCLUSIONSNVHL rats may be a valid animal model for schizophrenia. This strategy will be useful in future neurobiological studies investigating the etiology of schizophrenia.

Animals ; Animals, Newborn ; Central Nervous System ; drug effects ; physiopathology ; Evoked Potentials, Auditory ; drug effects ; Hippocampus ; drug effects ; physiopathology ; Ibotenic Acid ; toxicity ; Rats ; Schizophrenia ; chemically induced ; physiopathology ; Sensory Gating ; drug effects