Neuroscience
-
Previous work from our lab revealed that adult female rats have increased levels of myelin basic protein (MBP), a marker for myelination, in the orbitofrontal cortex (OFC) as compared to adult males. The goal of the present study was to determine the role of gonadal hormones, acting either in adulthood or at puberty, in the development of an adult sex difference in OFC levels of MBP. In an initial experiment, we replicated our previous results demonstrating that gonadally intact female rats have increased levels of MBP in the OFC as compared to males. ⋯ This reduction eliminated the sex difference in adult MBP levels in the OFC. These results reveal puberty to be an organizational time point for a sex difference in the OFC of adult rats in levels of a marker of myelination. This neuroanatomical difference may contribute to observed sex differences in OFC-associated behaviors including in inhibitory control.
-
A secondary consequence of spinal cord injury (SCI) is debilitating chronic neuropathic pain, which is commonly morphine resistant and inadequately managed by current treatment options. Consequently, new pain management therapies are desperately needed. We previously reported that dopamine D3 receptor (D3R) dysfunction was associated with opioid resistance and increases in D1 receptor (D1R) protein expression in the spinal cord. ⋯ Following SCI, morphine + pramipexole and morphine + SCH 39166 significantly increased both thermal and mechanical thresholds. Morphine alone induced conditioned place preference, but when combined with either the D3R agonist or D1R antagonist preference was not induced. The data suggest that adjunct therapy with receptor-specific dopamine modulators can restore morphine analgesia and decrease reward potential and thus, represents a new target for pain management therapy after SCI.
-
Substantia nigra pars reticulata is the output station in basal ganglia; its GABAergic neurons control the activity of thalamo-cortical premotor nuclei, thus controlling motor behavior. D1-like and D2-like presynaptic dopamine receptors on subthalamo-nigral afferents by modulation of glutamate release change the firing rate of nigral neurons; however, their relative contribution to the control of glutamate release and their pharmacological properties have not been studied. This is important since the prevalence of the inhibition or stimulation of release determines the firing rate of nigral neurons, therefore motor activity. ⋯ We also co-activated these to test their interaction; an antagonist interaction of D1-like with D2 and D3R, and an additive between D2 and D3R were found. Pharmacological receptor antagonist effects in release from reserpinized vs. non-reserpinized slices were similar, suggesting that endogenous dopamine stimulates receptors in the same way. These findings suggest differences in the control of glutamate release by different dopamine receptors in the substantia nigra, which could contribute to explaining the effect of dopamine and its agonists on motor behavior.
-
Schizophrenia is a severe mental disorder with numerous etiological susceptibilities. Maternal infection is a key risk factor for schizophrenia. Prenatal lipopolysaccharide (LPS) infection stimulates cytokine production that affects brain development. ⋯ The neuronal morphology of neurons in the VH in LPS-treated rats remained unaltered. Interestingly, the anxiogenic-related behavior correlated with neuronal hypertrophy observed in the BLA. Our findings suggest that the behavioral and neural modifications observed in our model could be mediated by the long-lasting alterations in Zn and NO levels in the brain.
-
Exploring sexual dimorphisms in the brain morphology is important for their impact and therapeutic implications for several neurological diseases. The hypothesis that sex could influence the transcriptome of brain cells could be the basis regarding the different response to cognitive decline identified in men and women. In this paper, we analyzed several prefrontal cortices (PFC) microarrays datasets of young/middle-aged healthy subjects and then Alzheimer's disease (AD) patients, according to the sex. ⋯ In addition, the sex-matched analysis of transcriptome identified a convergent molecular signature in men and women AD patients. Furthermore, the WPSEG belonging to CNS cells in PFC of healthy middle-aged subjects was correlated to AD profiles according to the sex. Since our results, it is possible to conclude that during the aging the PFC' cells adopt transcriptional strategies sex-dependent that could potentially control the development of neurodegenerative diseases.