Brain research
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Endoplasmic reticulum (ER) stress has been implicated in the pathology of cerebral ischemia. During prolonged period of stress or when the adaptive response fails, apoptotic cell death ensues. Cerebral ischemic postconditioning (Postcond) has been shown to reduce cerebral ischemia/reperfusion (I/R) injury in both focal and global cerebral ischemia model. ⋯ LY294002, a phosphoinositide 3-kinase inhibitor, increased the number of TUNEL-positive cells suppressed by Postcond in penumbra. In addition, LY294002 diminished the effect of Postcond on the activation of CHOP, caspase-12 and GRP78. These results suggest that Postcond protects brain from I/R injury by suppressing ER stress-induced apoptosis and PI3K/Akt pathway is involved.
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We used rapid event-related fMRI to explore factors modulating the activation of orthographic and phonological representations of print during a visual lexical decision task. Stimuli included homophonous word and nonword stimuli (MAID, BRANE), which have been shown behaviorally to produce longer response times due to phonological mediation effects. We also manipulated participants' reliance on orthography by varying the extent to which nonword foils were orthographically typical (wordlike context) or atypical (non-wordlike context) of real words. ⋯ Homophonous effects in the non-wordlike context were primarily isolated to medial extrastriate regions, hypothesized to be involved in low level visual processing and not reading-related processing per se. These findings demonstrate that the degree to which phonological and orthographic representations of print are activated depends not only on homophony, but also on the word-likeness of nonword stimuli. Implications for models of visual word recognition are discussed.
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The effects of estrogens on the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) are essential for its role in the regulation of female sexual behavior. Enhanced synaptogenesis and induction of progesterone receptors (PRs) are hallmarks of the actions of estrogens on the VMNvl. To investigate the influence of neural afferents in mediating these effects, we estimated the number of spine and dendritic synapses per neuron and the total number of PR-immunoreactive neurons in ovariectomized rats treated with either estradiol benzoate or vehicle, after unilateral VMN deafferentation. ⋯ The reduction was also visible, but less marked, in the contralateral VMNvl. Contrary to synapses, the estrogen induction of PRs was unaffected by deafferentation, and the total number of PR-immunoreactive neurons was similar in the control, deafferented and contralateral VMNvl. The results show that estrogens enhance synaptogenesis in the VMNvl by acting through neural afferents and induce PR expression by acting directly upon VMN neurons.
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This study assessed the potential of intravenous transplantation of human umbilical cord blood (HUCB) CD34+ cells transfected with glial cell line-derived neurotrophic factor (GDNF) gene to exert therapeutic benefits in spontaneous hypertensive rats (SHR) exposed to transient middle cerebral artery occlusion (MCAO). SHR with MCAO were randomly assigned to receive intravenously transplantation of vehicle, the plasmid containing the enhanced green fluorescent protein (pEGFP)-CD34+ cells or pEGFP-GDNF-CD34+ cells at 6h after stroke. ⋯ Furthermore, the stroke animals transplanted with GDNF gene modified CD34+ cells showed a significant increase in GDNF level in the infarcted hemisphere, reduced brain infarction volume, and enhanced functional recovery compared with those that received pEGFP-CD34+ cells. This study supports the use of a combined gene and stem cell therapy for treating stroke.
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Kisspeptin has recently been identified as a key neuroendocrine gatekeeper of reproduction and is essential for the initiation of human puberty and maintenance of adult reproduction. Kisspeptin neurons appear to be integrative sensors, as they respond to changes in numerous internal and external factors including nutrient and fat status, stress and sex steroids, thus providing a link between these factors and reproduction. ⋯ These demonstrate an essential role for kisspeptin in GnRH neuron firing, GnRH pulsatile secretion, negative feedback by gonadal steroids, the onset of puberty, and the ovulatory LH surge. These studies establish that kisspeptin antagonists are powerful investigative tools and set the scene for more extensive physiological and pathophysiological studies as well as therapeutic intervention.