Neuroscience
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The pedunculopontine nucleus (PPN) and central mesencephalic reticular formation (cMRF) both send projections and receive input from areas with known vestibular responses. Noting their connections with the basal ganglia, the locomotor disturbances that occur following lesions of the PPN or cMRF, and the encouraging results of PPN deep brain stimulation in Parkinson's disease patients, both the PPN and cMRF have been linked to motor control. In order to determine the existence of and characterize vestibular responses in the PPN and cMRF, we recorded single neurons from both structures during vertical and horizontal rotation, translation, and visual pursuit stimuli. ⋯ Directional preferences also differed between the PPN, which was preferentially modulated during nose-down pitch, and cMRF, which was preferentially modulated during ipsilateral yaw rotation. Finally, amplitude responses were similar between the PPN and cMRF during rotation and pursuit stimuli, but PPN responses to translation were of higher amplitude than cMRF responses. Taken together with their connections to the vestibular circuit, these results implicate the PPN and cMRF in the processing of vestibular stimuli and suggest important roles for both in responding to motion perturbations like falls and turns.
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Since homocysteine (Hcy) is considered a risk factor to cerebral diseases and adenine nucleotides are important molecules to brain normal function, in the present study we investigated the effect of chronic mild hyperhomocysteinemia on ectonucleotidase activities and expression in rat cerebral cortex. The levels of ATP, ADP, AMP and adenosine (Ado) in cerebrospinal fluid (CSF) of adult rats also were evaluated by high-performance liquid chromatography. For the chronic chemically induced mild hyperhomocysteinemia, Hcy (0.03 μmol/g of body weight) was administered subcutaneously from the 30th to the 60th day of life. ⋯ Results showed that Hcy significantly decreased nucleotide hydrolysis in the synaptosomal fraction and increased E-NTPDase1 and ecto-5'-nucleotidase transcripts in rat cerebral cortex. ATP levels were significantly increased, while Ado decreased in CSF of Hcy-treated rats. These findings suggest that the unbalance in ATP and Ado levels may be, at last in part, involved in the cerebral toxicity of mild hyperhomocysteinemia.
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Human acidic fibroblast growth factor (haFGF), a neurotrophin-like growth factor in the brain, plays important roles in the development, differentiation and regeneration of brain neurons, which makes it potential to treat Alzheimer's disease (AD). In this study, haFGF(14-154) and TAT-haFGF(14-154) (haFGF(14-154) fused with the cell-penetrating peptide transactivator of transcription protein transduction domain (TAT-PTD)) were intranasally administrated for 5 weeks to investigate the effects on senescence-accelerated mouse prone-8 (SAMP8) mice (a mouse model of AD). Results showed that TAT-PTD could increase the concentration of haFGF in the brain significantly, and TAT-haFGF(14-154) was more effective than haFGF(14-154) in the same dosage (300 μg/kg). ⋯ TAT-haFGF(14-154) also significantly reduced β-amyloid protein(1-42) (Aβ(1-42)) deposits as well as the levels of Aβ soluble forms in the mice brains and prevented the neurons from apoptosis. Besides, the oxidative stress impairment in the brain and serum was also ameliorated. The results suggest that TAT-haFGF(14-154) could attenuate the disease progression of SAMP8 AD mice, and the mechanism is related to the regulation of neurons microenvironment including neurotransmitters, Aβ pathology and oxidative stress.
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Recently there has been a widespread interest in the development of kappa opioid receptor (KOPR) ligands for treatment of pain, depression and anxiety, and prevention of stress-induced drug relapse. However, most of these preclinical studies have been conducted using male experimental animals. In the present study we examined if sex differences exist in neural activity induced by the KOPR agonist trans-(±)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl) benzeneacetamide methanesulfonate (U50,488H). ⋯ In addition, we observed a notable sex difference in the basolateral amygdala; in males, U50,488H induced an increase in immuno-positive cell numbers but a decrease in females. However, across other brain regions males were generally more sensitive to U50,488H-induced alterations than females. These results suggest the need to include female subjects in studies examining emotional responses to KOPR ligands.
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Several studies in rodents have shown that dysfunctions of the thalamic reticular nucleus (TRN) result in deficits of sensory gating and attentional processes, two core features of schizophrenia. TRN receives inputs from the prefrontal cortex (PFC) and hippocampal formation, two structures which send excitatory projections to the nucleus accumbens (NAcc) and are interconnected with the basolateral amygdala (BLA). Here we determined whether (and which) changes occurred four weeks after a TRN lesion in the dendritic morphology of pyramidal neurons of layers 3 and 5 of the PFC, neurons of ventral and dorsal hippocampus, BLA, and the medium spiny neurons of the NAcc. ⋯ We also evaluated the effects of TRN lesion on exploratory behavior assessed by hole-board test and locomotor activity induced by a novel environment. We found that TRN damage induced a reduction in the exploratory behavior measured by hole-board test with neuronal hypotrophy in PFC (layer 5), CA1 ventral hippocampus and NAcc neurons. Taken together, these data suggest that the behavioral and morphological effects of TRN lesion are, at least partially, mediated by limbic subregions with possible consequences for schizophrenia-related behaviors.