The concept of the brain cognitive reserve is derived from the well-acknowledged notion that the degree of brain damage does not always match the severity of clinical symptoms and neurological/cognitive outcomes.It ha...The concept of the brain cognitive reserve is derived from the well-acknowledged notion that the degree of brain damage does not always match the severity of clinical symptoms and neurological/cognitive outcomes.It has been suggested that the size of the brain(brain reserve) and the extent of neural connections acquired through life(neural reserve) set a threshold beyond which noticeable impairments occur.In contrast,cognitive reserve refers to the brain's ability to adapt and reo rganize stru cturally and functionally to resist damage and maintain function,including neural reserve and brain maintenance,resilience,and compensation(Verkhratsky and Zorec,2024).展开更多
Mice carrying mutant amyloid precursor protein and presenilin-1 genes （APP/PS1 double trans- genic mice） have frequently been used in studies of Alzheimer＇s disease; however, such studies have focused mainly on hip...Mice carrying mutant amyloid precursor protein and presenilin-1 genes （APP/PS1 double trans- genic mice） have frequently been used in studies of Alzheimer＇s disease; however, such studies have focused mainly on hippocampal and cortical changes. The severity of Alzheimer＇s disease is known to correlate with the amount of amyloid-13 protein deposition and the number of dead neurons in the locus coeruleus. In the present study, we assigned APP/PS1 double transgenic mice to two groups according to age： young mice （5-6 months old） and aged mice （16-17 months old）. Age-matched wild-type mice were used as controls. Immunohistochemistry for tyrosine hydroxylase （a marker of catecholaminergic neurons in the locus coeruleus） revealed that APP/PS1 mice had 23% fewer cells in the locus coeruleus compared with aged wild-type mice. APP/PS1 mice also had increased numbers of cell bodies of neurons positive for tyrosine hydroxylase, but fewer tyrosine hydroxylase-positive fibers, which were also short, thick and broken. Quantitative analysis using unbiased stereology showed a significant age-related increase in the mean volume of tyrosine hy- droxylase-positive neurons in aged APP/PS1 mice compared with young APP/PS1 mice. Moreover, the mean volume of tyrosine hydroxylase-positive neurons was positively correlated with the total volume of the locus coeruleus. These findings indicate that noradrenergic neurons and fibers in the locus coeruleus are predisposed to degenerative alterations in APP/PS1 double transgenic mice.展开更多
Stressful stimuli induced by immobilization are perceived as acute stress in rats. This acute stress activates corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN), resulting...Stressful stimuli induced by immobilization are perceived as acute stress in rats. This acute stress activates corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN), resulting in stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. The ventral ascending noradrenergic bundles (V-NAB) from the brainstem innervate the PVN. To investigate the relationship between the response of the HPA axis and the V-NAB, we examined changes in plasma corticosterone, the final output of the HPA axis, and extracellular noradrenaline (NA) in the PVN following immobilization stress in rats that received bilateral 6-hydroxydopamine (6-OHDA) lesions of the V-NAB. 6-OHDA microinjection into the V-NAB reduced the magnitude of the responses of plasma corticosterone and extracellular NA in the PVN following immobilization stress. Our results suggest that V-NAB innervation of the PVN is involved in immobilization stress-induced activation of the HPA axis.展开更多
Background Degeneration of the locus coeruleus(LC)noradrenergic system contributes to clinical symptoms in Alzheimer’s disease(AD)and Parkinson’s disease(PD).Diffusion magnetic resonance imaging(MRI)has the potentia...Background Degeneration of the locus coeruleus(LC)noradrenergic system contributes to clinical symptoms in Alzheimer’s disease(AD)and Parkinson’s disease(PD).Diffusion magnetic resonance imaging(MRI)has the potential to evaluate the integrity of the LC noradrenergic system.The aim of the current study was to determine whether the diffusion MRI-measured integrity of the LC and its tracts are sensitive to noradrenergic degeneration in AD and PD.Methods Post-mortem in situ T1-weighted and multi-shell diffusion MRI was performed for 9 AD,14 PD,and 8 control brain donors.Fractional anisotropy(FA)and mean diffusivity were derived from the LC,and from tracts between the LC and the anterior cingulate cortex,the dorsolateral prefrontal cortex(DLPFC),the primary motor cortex(M1)or the hippocampus.Brain tissue sections of the LC and cortical regions were obtained and immunostained for dopamine-beta hydroxylase(DBH)to quantify noradrenergic cell density and fiber load.Group comparisons and correlations between outcome measures were performed using linear regression and partial correlations.Results The AD and PD cases showed loss of LC noradrenergic cells and fibers.In the cortex,the AD cases showed increased DBH+immunoreactivity in the DLPFC compared to PD cases and controls,while PD cases showed reduced DBH+immunoreactivity in the M1 compared to controls.Higher FA within the LC was found for AD,which was correlated with loss of noradrenergic cells and fibers in the LC.Increased FA of the LC-DLPFC tract was correlated with LC noradrenergic fiber loss in the combined AD and control group,whereas the increased FA of the LC-M1 tract was correlated with LC noradrenergic neuronal loss in the combined PD and control group.The tract alterations were not correlated with cortical DBH+immunoreactivity.Conclusions In AD and PD,the diffusion MRI-detected alterations within the LC and its tracts to the DLPFC and the M1 were associated with local noradrenergic neuronal loss within the LC,rather than noradrenergic changes in the cortex.展开更多
Several studies showed that sex hormone receptors are in close relationship with classical neurotransmitter neurons especially catecholaminergic(CA) neurons. There are many gonadotrophin releasing hormone (GnRH) neuro...Several studies showed that sex hormone receptors are in close relationship with classical neurotransmitter neurons especially catecholaminergic(CA) neurons. There are many gonadotrophin releasing hormone (GnRH) neurons in hypothalamus and the medial preoptic area (MPO). Electrical stimulation of MPO can cause a rise in secretion展开更多
The effects of stimulating locus coeruleus (LC) on neuronal activity of cerebellar fastigial nucleus (FN) was investigated. Stimulation of LC elicited inhibitory, excitatory and biphasic (inhibition-excitation) respon...The effects of stimulating locus coeruleus (LC) on neuronal activity of cerebellar fastigial nucleus (FN) was investigated. Stimulation of LC elicited inhibitory, excitatory and biphasic (inhibition-excitation) responses from FN cells. The majority of responsive cells showed an inhibitory response with a latency of less than 10 ms. Injection of α adrenoreceptor antagonists phentolamine (ⅳ) could block the inhibitory response of FN cells to the LC stimulation, but propranolol (ⅳ), a β adrenoreceptor antagonist, could not. These results suggest that LC-cerebellar noradrenergic afferent fibers may be involved in the cerebellar sensorimotor integration process by exerting their modulatory action on the cerebellar nuclear cells’ activities.展开更多
文摘The concept of the brain cognitive reserve is derived from the well-acknowledged notion that the degree of brain damage does not always match the severity of clinical symptoms and neurological/cognitive outcomes.It has been suggested that the size of the brain(brain reserve) and the extent of neural connections acquired through life(neural reserve) set a threshold beyond which noticeable impairments occur.In contrast,cognitive reserve refers to the brain's ability to adapt and reo rganize stru cturally and functionally to resist damage and maintain function,including neural reserve and brain maintenance,resilience,and compensation(Verkhratsky and Zorec,2024).
基金supported by the National Natural Science Foundation of China, No. 81100663the Scientific Research Funds of the Health Department of Hunan Province, No.120303+1 种基金Hunan Provincal Natural Science Foundation of China, No. 13JJ3058a grant from the Scientific Research Program of Hunan Provincial Higher Education Institutes, No. 11C0829
文摘Mice carrying mutant amyloid precursor protein and presenilin-1 genes （APP/PS1 double trans- genic mice） have frequently been used in studies of Alzheimer＇s disease; however, such studies have focused mainly on hippocampal and cortical changes. The severity of Alzheimer＇s disease is known to correlate with the amount of amyloid-13 protein deposition and the number of dead neurons in the locus coeruleus. In the present study, we assigned APP/PS1 double transgenic mice to two groups according to age： young mice （5-6 months old） and aged mice （16-17 months old）. Age-matched wild-type mice were used as controls. Immunohistochemistry for tyrosine hydroxylase （a marker of catecholaminergic neurons in the locus coeruleus） revealed that APP/PS1 mice had 23% fewer cells in the locus coeruleus compared with aged wild-type mice. APP/PS1 mice also had increased numbers of cell bodies of neurons positive for tyrosine hydroxylase, but fewer tyrosine hydroxylase-positive fibers, which were also short, thick and broken. Quantitative analysis using unbiased stereology showed a significant age-related increase in the mean volume of tyrosine hy- droxylase-positive neurons in aged APP/PS1 mice compared with young APP/PS1 mice. Moreover, the mean volume of tyrosine hydroxylase-positive neurons was positively correlated with the total volume of the locus coeruleus. These findings indicate that noradrenergic neurons and fibers in the locus coeruleus are predisposed to degenerative alterations in APP/PS1 double transgenic mice.
文摘Stressful stimuli induced by immobilization are perceived as acute stress in rats. This acute stress activates corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN), resulting in stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. The ventral ascending noradrenergic bundles (V-NAB) from the brainstem innervate the PVN. To investigate the relationship between the response of the HPA axis and the V-NAB, we examined changes in plasma corticosterone, the final output of the HPA axis, and extracellular noradrenaline (NA) in the PVN following immobilization stress in rats that received bilateral 6-hydroxydopamine (6-OHDA) lesions of the V-NAB. 6-OHDA microinjection into the V-NAB reduced the magnitude of the responses of plasma corticosterone and extracellular NA in the PVN following immobilization stress. Our results suggest that V-NAB innervation of the PVN is involved in immobilization stress-induced activation of the HPA axis.
文摘Background Degeneration of the locus coeruleus(LC)noradrenergic system contributes to clinical symptoms in Alzheimer’s disease(AD)and Parkinson’s disease(PD).Diffusion magnetic resonance imaging(MRI)has the potential to evaluate the integrity of the LC noradrenergic system.The aim of the current study was to determine whether the diffusion MRI-measured integrity of the LC and its tracts are sensitive to noradrenergic degeneration in AD and PD.Methods Post-mortem in situ T1-weighted and multi-shell diffusion MRI was performed for 9 AD,14 PD,and 8 control brain donors.Fractional anisotropy(FA)and mean diffusivity were derived from the LC,and from tracts between the LC and the anterior cingulate cortex,the dorsolateral prefrontal cortex(DLPFC),the primary motor cortex(M1)or the hippocampus.Brain tissue sections of the LC and cortical regions were obtained and immunostained for dopamine-beta hydroxylase(DBH)to quantify noradrenergic cell density and fiber load.Group comparisons and correlations between outcome measures were performed using linear regression and partial correlations.Results The AD and PD cases showed loss of LC noradrenergic cells and fibers.In the cortex,the AD cases showed increased DBH+immunoreactivity in the DLPFC compared to PD cases and controls,while PD cases showed reduced DBH+immunoreactivity in the M1 compared to controls.Higher FA within the LC was found for AD,which was correlated with loss of noradrenergic cells and fibers in the LC.Increased FA of the LC-DLPFC tract was correlated with LC noradrenergic fiber loss in the combined AD and control group,whereas the increased FA of the LC-M1 tract was correlated with LC noradrenergic neuronal loss in the combined PD and control group.The tract alterations were not correlated with cortical DBH+immunoreactivity.Conclusions In AD and PD,the diffusion MRI-detected alterations within the LC and its tracts to the DLPFC and the M1 were associated with local noradrenergic neuronal loss within the LC,rather than noradrenergic changes in the cortex.
文摘Several studies showed that sex hormone receptors are in close relationship with classical neurotransmitter neurons especially catecholaminergic(CA) neurons. There are many gonadotrophin releasing hormone (GnRH) neurons in hypothalamus and the medial preoptic area (MPO). Electrical stimulation of MPO can cause a rise in secretion
文摘The effects of stimulating locus coeruleus (LC) on neuronal activity of cerebellar fastigial nucleus (FN) was investigated. Stimulation of LC elicited inhibitory, excitatory and biphasic (inhibition-excitation) responses from FN cells. The majority of responsive cells showed an inhibitory response with a latency of less than 10 ms. Injection of α adrenoreceptor antagonists phentolamine (ⅳ) could block the inhibitory response of FN cells to the LC stimulation, but propranolol (ⅳ), a β adrenoreceptor antagonist, could not. These results suggest that LC-cerebellar noradrenergic afferent fibers may be involved in the cerebellar sensorimotor integration process by exerting their modulatory action on the cerebellar nuclear cells’ activities.
