Objective:To investigate the neural regulatory mechanism of parvalbumin-positive interneurons(PV-INs)in the dentate gyrus(DG)involved in the impairment of spatial recognition memory by exercise-induced chronic fatigue.Methods:Male Sprague-Dawley(SD)rats were divided into control group and fatigue group by random num-ber method.A three-level incremental load treadmill training program was selected to establish a chronic exhaustion exercise fatigue model.The spatial recognition memory ability of rats was tested by novel object recognition test.The ac-tivation levels and quantitative changes of astrocytes(AS)and PV-INs in the DG region was observed and quantified through immunofluorescence staining and immunohistochemical staining.The phosphorylation level of calcium/calmodu-lin-dependent protein kinase Ⅱ(CaMK Ⅱ)in the hippocampus was detected by Western blot.Results:In the test of novel object recognition,the exploration time of novel object was reduced in the fatigue group,and the discrimination index was significantly lower than that in the control group(P＜0.01).Immunohistochemical staining showed that PV-INs in the DG region of fatigue rats were lighter and fewer than those in the control group,the fibers were short and sparse,and the positive cell density and average optical density of cells were significantly lower than those in the control group(P＜0.01).Immunofluorescence staining showed that AS was significantly activated,glial fibrillary acidic pro-tein(GFAP)was stained deeply,and the cell processes were dense and elongated in the DG region of fatigue rats.The positive cell density and mean fluorescence intensity were significantly higher than those of the control group(P＜0.01).The results of Western blot showed that the phosphorylation level of CaMK Ⅱ protein in the hippocampus of the fatigue group was significantly reduced than that of the control group(P＜0.01).Conclusion:Exercise-induced chro-nic fatigue inhibited PV-INs in the rat hippocampal DG region.The excessive activation of AS following exercise fatigue may be a major contributor to this PV-INs suppression.Concurrently,reduced phosphorylation levels of CaMK Ⅱ protein were observed in hippocampal tissue.These alterations ultimately impaired spatial recognition memory in the rats.

Objective:To investigate the neural regulatory mechanism of parvalbumin-positive interneurons(PV-INs)in the dentate gyrus(DG)involved in the impairment of spatial recognition memory by exercise-induced chronic fatigue.Methods:Male Sprague-Dawley(SD)rats were divided into control group and fatigue group by random num-ber method.A three-level incremental load treadmill training program was selected to establish a chronic exhaustion exercise fatigue model.The spatial recognition memory ability of rats was tested by novel object recognition test.The ac-tivation levels and quantitative changes of astrocytes(AS)and PV-INs in the DG region was observed and quantified through immunofluorescence staining and immunohistochemical staining.The phosphorylation level of calcium/calmodu-lin-dependent protein kinase Ⅱ(CaMK Ⅱ)in the hippocampus was detected by Western blot.Results:In the test of novel object recognition,the exploration time of novel object was reduced in the fatigue group,and the discrimination index was significantly lower than that in the control group(P＜0.01).Immunohistochemical staining showed that PV-INs in the DG region of fatigue rats were lighter and fewer than those in the control group,the fibers were short and sparse,and the positive cell density and average optical density of cells were significantly lower than those in the control group(P＜0.01).Immunofluorescence staining showed that AS was significantly activated,glial fibrillary acidic pro-tein(GFAP)was stained deeply,and the cell processes were dense and elongated in the DG region of fatigue rats.The positive cell density and mean fluorescence intensity were significantly higher than those of the control group(P＜0.01).The results of Western blot showed that the phosphorylation level of CaMK Ⅱ protein in the hippocampus of the fatigue group was significantly reduced than that of the control group(P＜0.01).Conclusion:Exercise-induced chro-nic fatigue inhibited PV-INs in the rat hippocampal DG region.The excessive activation of AS following exercise fatigue may be a major contributor to this PV-INs suppression.Concurrently,reduced phosphorylation levels of CaMK Ⅱ protein were observed in hippocampal tissue.These alterations ultimately impaired spatial recognition memory in the rats.

GAP-43,netrin-1,collapsin-1,and neuropilin-1 have been regarded to play crucial roles in the formation of patterned neural connections.The cerebellum consists of five distinct concentric layers:white matter,internal granule layer (IGL),Purkinje cell layer (PCL),molecular layer (ML),and external granule layer (EGL) in young rodents.Cells in EGL are generated after birth.In contrast Purkinje neurons are born before birth,which receive main innervations of climbing fibers fi'om the inferior olivary nucleus and parallel fibers from the internal granule cells.These innervations are mostly established in the first three postnatal weeks,accompanying the sprouting and maturation of Purkinje cells.The potential roles of GAP-43,netrin-1,collapsin-1 and neuropilin-1 in the postnatal development of cerebellum remain unclear.To get insights into the above issue,the expression of GAP-43,netrin-1,collapsin-1,and neuropilin-1 mRNAs and proteins were examined in the cerebellum of mice at postnatal days (P) 5,P10,P20 and adulthood.The results showed that these four molecules were expressed in different temporal and spatial patterns in the postnatal cerebellum of mice,which was in match with axonal synaptogenesis,elongation and synapse formation during postnatal development and adulthood.By using double immunohistocbemistry,it was found that the Purkinje cells stained for GAP-43 were also positive for either netrin-1 or collapsin-1 at P10,and cells stained for collapsin-1 were also positive for netrin-1 or neuropilin-1.It was suggested that the four molecules are involved in the postnatal development of cerebellum.