Parallel declines in fos activation of the medial anteroventral periventricular nucleus and LHRH neurons in middle-aged rats

The middle-age decline in reproductive function is manifested by reduced LH RH release, resulting in a decreased magnitude and delay of onset of the LH surge. Earlier studies suggested that the reductions in LHRH neural activa tion in middle-aged rats resulted from deficits in the afferent drive to th e LHRH neurons. One critical afferent to the LHRH neurons lies in the anter oventral periventricular preoptic area (AVPv) nucleus. The neurons of the m edial AVPv are synchronously activated to express Fos with LHRH neurons at the time of an LH surge in young adult animals. The present study examined whether, in middle age, reductions in the activation of AVPv neurons accomp any the reduction in Fos activation in LHRH neurons. Young (3- to 4-month-old) and middle-aged (10- to 12-month-old) spontaneous ly cycling and ovariectomized steroid-replaced rats were killed during peak and early descending phase of the LH surge, and their brains were examined for Fos in LHRH and AVPv neurons. Young animals had a characteristic incre ase in Fos expression in both LHRH and AVPv neurons. In middle-aged rats, t he proportion of LHRH neurons expressing Fos at the time of an LH surge was reduced by approximately 50%, irrespective of whether surges were spontane ous or induced by exogenous steroids. A similar reduction in the number of Fos+ cells (by approximately 50%) was noted in the medial AVPv. Linear regression analysis of the relationship be tween the extent of Fos activation in LHRH and AVPv neurons revealed a stro ng positive correlation (r(2) = 0.66; P < 0.01), suggesting that changes in the AVPv's drive to LHRH neurons underlie the decrease in LHRH activity in middle age. A second series of experiments examined whether decreased input from the AV Pv could account for reduced Fos activation in LHRH neurons seen in middle- aged animals. When the medial AVPv was lesioned, LHRH neurons failed to exp ress Fos on the side ipsilateral to the lesion. Animals with lesioned media l AVPv also had significantly lower LH values than animals with an intact m edial AVPv. Taken together, these data suggest that a principal deficit in middle-aged rats is the ability of the medial AVPv to stimulate LHRH neuron s.