Martin William Moore Prentice.

Initially a practitioner, he later joined the Meat Hygiene Service inspecting and approving slaughterhouses. After retirement he was ordained in the Church of Scotland and served remote island communities.

Neurosteroids: endogenous allosteric modulators of GABA(A) receptors.

In the mammalian central nervous system activation of the ionotropic GABA(A) receptor by the neurotransmitter GABA plays a crucial role in controlling neuronal excitability. This essential form of neuronal regulation may be subject to "fine tuning" by particular metabolites of progesterone and deoxycorticosterone, which bind directly to the GABA(A) receptor to enhance the actions of GABA. Originally such steroids were considered to act as endocrine messengers, being synthesised in peripheral glands such as the adrenals and ovaries and crossing the blood brain barrier to influence neuronal signalling. However, it is now evident that certain neurons and glia may produce such "neurosteroids" and that these locally synthesised modulators may act in a paracrine, or indeed an autocrine manner to influence neuronal activity. Neurosteroid synthesis may change dynamically in a variety of physiological situations (e.g. stress, pregnancy) and perturbations in their levels are implicated in a variety of neurological and psychiatric disorders. Here we will consider (1) evidence supporting the concept that neurosteroids act as local regulators of neuronal inhibition, (2) that extrasynaptic GABA(A) receptors appear to be a particularly important neurosteroid target and (3) recent advances in defining the neurosteroid binding site(s) on the GABA(A) receptor.

Spermatozoa have decreased antioxidant enzymatic capacity and increased reactive oxygen species production during aging in the Brown Norway rat.

As the proportion of aged males attempting to reproduce continues to rise, so does the concern regarding the quality of spermatozoa from aged men. An imbalance between the generation of reactive oxygen species (ROS) and cellular antioxidant defenses, as occurs in aging, ultimately leads to decreased protein, lipid, and DNA quality. Spermatozoa are highly susceptible to oxidative damage, and thus an age-related shift in redox status may have serious implications for fertility. Therefore, we examined the effect of age on antioxidant enzymatic activity, ROS production, and extent of lipid peroxidation in both caput and cauda epididymal spermatozoa from young (4-month-old) and old (21-month-old) Brown Norway rats. Glutathione peroxidase (Gpx1, Gpx4) and superoxide dismutase (SOD) enzymes had decreased activity in aging spermatozoa. Immunofluorescence studies indicated that Gpx4 expression was decreased in both the head and midpiece regions of spermatozoa in aged animals. The decrease in nuclear Gpx4 points to a novel potential mechanism that may explain the previously noted decreased levels of protamine disulfide bonds in aged sperm nuclei. Further, hydrogen peroxide (H2O2) and superoxide (O2(.-)) production were increased significantly in aging spermatozoa. Finally, lipid peroxidation was found to be drastically increased in aged spermatozoa. Taken together, these results suggest a decreased capacity for aged spermatozoa to handle oxidative stress and provide a potential basis for understanding the underlying cause of decreased quality of spermatozoa during aging.