Neuroscience
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While the acute physiological effects of brain-derived neurotrophic factor (BDNF) have been well demonstrated, little is known regarding possible morphological effects that occur within a short period of time. The acute effects of BDNF on dendritic spine morphology were examined in granule cells in cultured main olfactory bulb slices. Organotypic slices prepared from 7-day-old rats were cultured for 1 day, and BDNF was applied at varying time points prior to fixation. ⋯ The changes became detectable as early as 30 min when 50 ng of BDNF was applied. The pretreatment with tetanus toxin or an N-methyl-D-aspartate receptor antagonist abolished the acute effects of BDNF on spine morphology. These results indicate that BDNF can alter spine morphology within a shorter period of time than previously observed and that the effects are mediated by enhanced glutamatergic signaling.
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Recent studies indicate that brain-derived neurotrophic factor (BDNF) may be implicated in the clinical action of antidepressant drugs. Repeated (2-3 weeks) administration of antidepressant drugs increases BDNF gene expression. The onset of this response as well as concomitant effects on the corresponding BDNF protein is however, unclear. ⋯ Indicative of the highly regional change within the hippocampus, the ELISA method failed to demonstrate significant up-regulation at 21 days, measuring levels of BDNF protein in the whole hippocampus. In contrast to the detected time dependent and biphasic response of the BDNF gene, activity-regulated, cytoskeletal-associated protein (Arc) mRNA showed a gradual increase during the 14-day course of treatment. The results presented here show that BDNF is expressed differentially depending on length of fluoxetine administration, which could contribute in explaining the slow onset of antidepressant activity observed with selective serotonin reuptake inhibitors.
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Tg2576 transgenic mice (mice overexpressing the "Swedish" mutation in the human amyloid precursor protein 695) demonstrated a decreased capacity for cell proliferation in the dentate gyrus of the hippocampus compared with non-transgenic littermates at 3 months, 6 months and 9 months of age. Isolation stress induced by individually housing each mouse from the time of weaning further decreased hippocampal cell proliferation in Tg2576 mice as well as in non-transgenic littermates at 6 months of age. Decreases in hippocampal cell proliferation in isolated Tg2576 mice were associated with impairments in contextual but not cued memory. ⋯ These results suggest that Tg2576 mice, a mouse model of Alzheimer disease, have an impaired ability to generate new cells in the dentate gyrus of the hippocampus and that the magnitude of this impairment can be modulated by behavioral interventions and drugs known to have effects on hippocampal neurogenesis in normal rodents. Unexpectedly, isolation stress also appeared to accelerate the underlying process of beta-amyloid plaque deposition in Tg2576 mice. These results suggest that stress may have an impact on the underlying disease process associated with Alzheimer's disease.
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Although gender differences in the response to stress have been reported, differences in stress-induced changes in feeding behavior have not been well studied. In this report, inhibition of food intake was compared in male and female rats following 1 h of restraint, electric footshock, or emotional stress induced by a communication box. Although the three stressors inhibited food intake in both genders, only emotional stress caused a gender difference, a greater inhibition of food intake in female rats (48%) than in male rats (22%). ⋯ Ovariectomy reduced the inhibition of food intake by emotional stress to the same level as that in male, and replacement with estradiol restored the inhibition to the level of the normal female rats. A corticotropin-releasing factor (CRF) type 1 receptor antagonist prevented emotional stress-induced inhibition of food intake, indicating the involvement of CRF type 1 receptor in emotional stress-induced inhibition of food intake. These results suggest that female rats show a greater inhibition of food intake in response to emotional stress than male rats and that estrogen plays a role in the gender difference.
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In some brain regions, previous studies reported the frequent coexistence between neuronal nitric oxide synthase (nNOS) and somatostatin (SOM). In the hippocampus, nNOS and SOM were mainly expressed in GABAergic nonprincipal neurons. Here we estimated the immunocytochemical colocalization of nNOS and SOM in the mouse hippocampus using the optical disector. ⋯ On the other hand, the percentages of SOM-LIR neurons containing nNOS immunoreactivity were somewhat high in the stratum lucidum of the dorsal CA3 region (19%) and dorsal dentate hilus (28%), whereas they were very low in the other layers. Immunofluorescent triple labeling of axon terminals for nNOS, SOM and glutamic acid decarboxylase indicated that some nNOS-IR/SOM-LIR neurons might be dendritic inhibitory cells. The present results show the infrequent colocalization of nNOS and SOM in the mouse hippocampus, and also suggest that the double-labeled cells may be a particular subpopulation of hippocampal GABAergic nonprincipal neurons.