Exposure to ethanol during neurodevelopment modifies crucial offspring rat brain enzyme activities in a region-specific manner.

The experimental simulation of conditions falling within "the fetal alcohol spectrum disorder" (FASD) requires the maternal exposure to ethanol (EtOH) during crucial neurodevelopmental periods; EtOH has been linked to a number of neurotoxic effects on the fetus, which are dependent upon the extent and the magnitude of the maternal exposure to EtOH and for which very little is known with regard to the exact mechanism(s) involved. The current study has examined the effects of moderate maternal exposure to EtOH (10 % v/v in the drinking water) throughout gestation, or gestation and lactation, on crucial 21-day-old offspring Wistar rat brain parameters, such as the activities of acetylcholinesterase (AChE) and two adenosine triphosphatases (Na(+),K(+)-ATPase and Mg(2+)-ATPase), in major offspring CNS regions (frontal cortex, hippocampus, hypothalamus, cerebellum and pons). The implemented experimental setting has provided a comparative view of the neurotoxic effects of maternal exposure to EtOH between gestation alone and a wider exposure timeframe that better covers the human third trimester-matching CNS neurodevelopment period (gestation and lactation), and has revealed a CNS region-specific susceptibility of the examined crucial neurochemical parameters to the EtOH exposure schemes attempted. Amongst these parameters, of particular importance is the recorded extensive stimulation of Na(+),K(+)-ATPase in the frontal cortex of the EtOH-exposed offspring that seems to be a result of the deleterious effect of EtOH during gestation. Although this stimulation could be inversely related to the observed inhibition of AChE in the same CNS region, its dependency upon the EtOH-induced modulation of other systems of neurotransmission cannot be excluded and must be further clarified in future experimental attempts aiming to simulate and to shed more light on the milder forms of the FASD-related pathophysiology.

Gestational exposure to cadmium alters crucial offspring rat brain enzyme activities: the role of cadmium-free lactation.

The present study aimed to shed more light on the effects of gestational (in utero) exposure to cadmium (Cd) on crucial brain enzyme activities of Wistar rat offspring, as well as to assess the potential protective/restorative role that a Cd-free lactation might have on these effects. In contrast to earlier findings of ours regarding the pattern of effects that adult-onset exposure to Cd has on brain AChE, Na(+),K(+)- and Mg(2+)-ATPase activities, as well as in contrast to similar experimental approaches implementing the sacrificing mode of anaesthesia, in utero exposure to Cd-chloride results in increased AChE and Na(+),K(+)-ATPase activities in the newborn rat brain homogenates that were ameliorated through a Cd-free lactation (as assessed in the brain of 21-day-old offspring). Mg(2+)-ATPase activity was not found to be significantly modified under the examined experimental conditions. These findings could provide the basis for a further evaluation of the herein discussed neurotoxic effects of in utero exposure to Cd, in a brain region-specific manner.

Activation of acetylcholinesterase after U-74389G administration in a porcine model of intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) accounts for 10-15% of all strokes. Despite high incidence, morbidity and mortality, the precise pathophysiology of spontaneous ICH is not fully understood, while there is little data concerning the mechanisms that follow the primary insult of the hematoma formation. The cholinergic system, apart from its colossal importance as a neurotransmission system, seems to also play an important role in brain injury recovery. It has been recently suggested that the brain possesses a cholinergic anti-inflammatory pathway that counteracts the inflammatory responses after ICH, thereby limiting damage to the brain itself. We, herein, report the findings of our study concerning the role of acetylcholinesterase (AChE; a crucial membrane-bound enzyme involved in cholinergic neurotransmission) in a porcine model of spontaneous ICH, with a focus on the first 4 and 24 h following the lesion's induction, in combination with a study of the effectiveness of the lazaroid antioxidant U-74389G administration. Our study demonstrates the activation of AChE activity following U-74389G administration. The lazaroid U-74389G seems to be an established neuroprotectant and this is the first report of its supporting role in the enhancement of cholinergic response to the induction of ICH.

The regulatory role of neurotensin on the hypothalamic-anterior pituitary axons: emphasis on the control of thyroid-related functions.

Neurotensin (NT) is a 13 amino acid neurohormone and/or neuromodulator, located in the synaptic vesicles and released from the neuronal terminals in a calcium-dependent manner. This peptide is present among mammalian and nonmammalian species, mainly in the central nervous system and the gastrointestinal tract. Due to its neuroendocrine activity, NT has been related to the pathophysiology of a series of disorders, such as schizophrenia, drug-abuse, Parkinson's disease, cancer, stroke, eating disorders and other neurodegenerative conditions. Moreover, NT participates in the physiology of pain-induction, central blood pressure control and inflammation. NT also plays an important interactive role in all components of the hypothalamic-anterior pituitary circuit, which is mediated by an endocrine, paracrine or/and autocrine manner, towards most of the anatomical regions that define this circuit. A considerable amount of data implicates NT in thyroid-related regulation through this circuit, the exact mechanisms of which should be further investigated for the potential development of more targeted approaches towards the treatment of thyroid-related endocrine diseases. The aim of this study was to provide an up-to-date review of the literature concerning the regulatory role of NT on the hypothalamic-anterior pituitary axons, with an emphasis on the control of thyroid-related functions.