Neuroscience
-
Studies have shown a few cerebral metabolites modified by cocaine in brain regions; however, endogenous metabolic profiling has been lacking. Ex vivo (1)H NMR (hydrogen-1 nuclear magnetic resonance) spectroscopy-based metabonomic approach coupled with partial least squares was applied to investigate the changes of cerebral metabolites in nucleus accumbens (NAc) and striatum of rats subjected to cocaine treatment. Our results showed that both single and repeated cocaine treatment can induce significant changes in a couple of cerebral metabolites. ⋯ Moreover, groups of rats with and without conditioned place preference (CPP) apparatus are presenting difference in metabolites. Collectively, our results provide the first evidence of metabonomic profiling of NAc and striatum in response to cocaine, exhibiting a regionally-specific alteration patterns. We find that repeated cocaine administration leads to significant metabolite alterations, which are involved in neurotransmitter disturbance, oxidative stress, mitochondria dysregulation and membrane disruption in brain.
-
Rats repeatedly exposed to variable prenatal stress (PNS) exhibit schizophrenia-like behavioral signs such as social withdrawal, elevations in amphetamine-induced locomotor activity, deficits in sensory-motor gating, as well as impairments in memory-related task performance. However, to date there have been no studies designed to test the hypothesis that variable PNS would lead to disruptions in sustained attention and inhibitory response control (i.e., symptoms also commonly observed in schizophrenia and other neuropsychiatric disorders such as attention-deficit hyperactivity disorder). In the current study, the effects of variable PNS in rats were evaluated in fixed and variable stimulus duration (VSD) as well as variable intertrial interval (VITI) versions of a 5-choice serial reaction time task (5C-SRTT). ⋯ In contrast, atomoxetine decreased premature and timeout responses in both PNS and control subjects in the VITI version of the task and improved accuracy in the PNS subjects. The results suggest that exposure to variable PNS in rats results in impairments of sustained attention and inhibitory response control and that these deficits can be exacerbated by NMDA antagonism and improved by a norepinephrine uptake inhibitor. Collectively, these data further support the premise that variable PNS in rats is a valid model system for the study of neuropsychiatric disorders and their treatment.
-
Synapses are essential to neuronal functions. Synaptic changes occur under physiological and pathological conditions. Here we report the remodeling of synapses in the CA1 area of the hippocampus after transient global ischemia using electron microscopy. ⋯ Among asymmetric synapses, the number of perforated synapses consistently increased and reached a peak (approximately 10-fold increase) at 48 h after ischemia. On the other hand, the number of multiple synaptic boutons decreased after ischemia reaching a two to fourfold decrease at 48 h after ischemia. These results have shown that ischemia induces an increase of asymmetric synapses as well as synaptic autophagy, which may contribute to the neuronal death in the CA1 area after transient global ischemia.
-
Reactive gliosis has been implicated in injury and recovery patterns associated with hydrocephalus. The roles that these mechanisms play in the pathophysiology of hydrocephalus are still not clear in terms of cytopathology and gene expression. In this paper, we investigated the relationship between reactive gliosis and neuroinflammation of hydrocephalic rats of different severity at both cellular and molecular levels. Therefore 35 adult SD (standard deviation) rats were randomly divided into the normal group (n=5), the sham operation group (n=5) and the model group (n=25). Hydrocephalic rat models were induced by intraventricular injections of 3% kaolin, and the ventricular dilatation was examined by MRI (magnetic resonance imaging) at 2-week postoperation. Then the model group was subdivided into the mild group (n=5), the moderate group (n=7) and the severe group (n=9) according to the degree of ventricular dilatation. While IL-18 (interlukin 18), GFAP (glial fibrillary acidic protein), and Iba-1 (ionized calcium binding adaptor molecule-1) were detected by ELISA (enzyme-linked immunosorbent assay), RT-PCR, immunohistochemistry, Western blot and correlation analysis were conducted at the same time. According to the result comparison between the normal group and the sham operation group, the ventricle of model group was obviously enlarged (P<0.01). The expression of GFAP and Iba-1 was increased (P<0.05) in brain tissue of the model group and IL-18 was also increased in CSF (cerebrosinal fluid) sample of model group. It was revealed by correlation analysis that the increase was positively correlated with the severity of ventricular dilatation. ⋯ These results indicate that gliosis and inflammation continue to rise dramatically in experimental hydrocephalus and can be regarded as the main factors of hydrocephalus. Regulating the level of gliosis and alleviating inflammation may provide new therapeutic methods of hydrocephalus.
-
Cholinergic neurotransmission in the hippocampus is involved in cognitive functions, including learning and memory. Strategies to enhance septohippocampal cholinergic neurotransmission may therefore be of therapeutic value to limit cognitive decline during cholinergic dysfunction. In addition to current strategies being developed, such as the use of acetylcholinesterase inhibitors, enhancing acetylcholine (ACh) release may be critical for optimal cholinergic neurotransmission. ⋯ VAChT overexpression enhanced the release of ACh from ex vivo hippocampal slices. From these findings, we conclude that VAChT overexpression is sufficient to enhance ACh release in the hippocampal formation. It remains to be established whether, in cases of cholinergic deficits, increasing VAChT expression would re-establish adequate levels of cholinergic neurotransmission, thereby providing a valid therapeutic target.