Neuroprotective effects of estrogen therapy for cognitive and neurobiological profiles of monkey models of menopause.

Many postmenopausal women question whether to start or continue hormone therapy because of recent clinical trial negative results. However, evidence from other studies of postmenopausal women, and from studies in menopausal monkeys, indicate that estrogen has neurocognitive protective effects, particularly when therapy is initiated close to the time of menopause before neural systems become increasingly compromised with age. In this review, we present studies of menopausal women and female monkeys that support the concept that estrogen therapies protect both cognitive function and neurobiological processes.

Effects of two years of conjugated equine estrogens on cholinergic neurons in young and middle-aged ovariectomized monkeys.

The effect of estrogen on the number and size of cholinergic neurons in the basal forebrain was examined in surgically menopausal young and middle-aged cynomolgus monkeys. Young and middle-aged female monkeys were ovariectomized and treated with conjugated equine estrogens (Premarin) at doses that are equivalent to those currently prescribed to postmenopausal women. In the medial septum/diagonal band (MS/DB), no effect of treatment with Premarin was observed in the cholinergic neurons in either ovariectomized young or middle-aged monkeys. However, the number and size of cholinergic neurons in the MS/DB of middle-aged monkeys was greater than that in the young monkeys. In the nucleus basalis of Meynert (NBM) of middle-aged monkeys, the number of cholinergic neurons in the intermediate region (Ch4i) was greater in Premarin-treated monkeys as compared to controls and numbers of neurons in this region were greater at higher levels of estrogen. No effects of estrogen were observed in other NBM regions in the middle-aged monkeys and the size of cholinergic neurons was unaffected by Premarin. These findings suggest that treatment with Premarin has selective beneficial effects on cholinergic neurons in the basal forebrain but that these effects are both age and region specific.

Extracellular heat shock protein 70 has novel functional effects on sea urchin eggs and coelomocytes.

Numerous reports document that the 70 kDa heat shock proteins are not only intracellular proteins but are also present in blood and other extracellular compartments. How they affect cell function from the extracellular space remains unclear. Using two well-characterized cell types from the sea urchin, we show that extracellular mixtures of the constitutive and inducible forms of the 70 kDa heat shock proteins (Hsc70 and Hsp70, respectively) have dramatic effects on initiation of cell division in fertilized eggs and on the clotting reaction of hypotonically stressed coelomocytes. In suspensions of fertilized eggs to which Hsc70 or a 2:3 mixture of Hsc and Hsp70 was added, progression to the first mitotic division was accelerated. Evidence is provided that the extracellular Hsc70 passes into the egg cells in an unconventional manner, being distributed through the cytoplasm, and that it may alter the intracellular signaling cascade initiated by sperm penetration. In coelomocytes that were stimulated by hypotonic shock to mimic injury, the spreading reaction of the clotting response was significantly inhibited when either Hsp70 or Hsc70 was in the medium. These results suggest that the presence of Hsc and/or Hsp70 in the extracellular fluid may promote mitosis of dividing cells and suppress the reactivity of immune system cells.