Chronic hyponatremia reduces survival of magnocellular vasopressin and oxytocin neurons after axonal injury

Abstract

Axonal injury to hypothalamic magnocellular vasopressin (AVP) and oxytocin (OT) neurons causes degeneration of a substantial subpopulation of these neurons. In this study, we investigated the influence of osmolality on this injury-induced cell death. Normonatremic, chronically hypernatremic, and chronically hyponatremic rats received pituitary stalk compression (SC), which causes degeneration of AVP and OT terminals in the neurohypophysis. Twenty-one days after SC, rats were perfused and hypothalami were serially sectioned and alternately stained for AVP-neurophysin and OT-neurophysin immunoreactivities. Normonatremic and hypernatremic rats exhibited a triphasic pattern of water intake after SC, with peak intakes 3 times higher than those exhibited by sham-operated normonatremic rats. In contrast, hyponatremic SC rats exhibited peak water intakes of 600 ml/24 hr, approximately 9-10 times the water intakes of sham-operated normonatremic rats. In normonatremic rats, SC caused degeneration of 65% of the AVP neuron population in the SON and 73% in the PVN, but only 31% of the OT neuron population in the SON and 35% in the PVN. Similar results were found in hypernatremic rats after SC. However, in hyponatremic rats SC caused degeneration of 97% of the AVP neuron population in the SON and 93% in the PVN, and 90% of the OT neuron population in the SON and 84% in the PVN. Our results, therefore, demonstrate that injury-induced degeneration of magnocellular AVP and OT neurons is markedly exacerbated by chronic hypo-osmolar conditions, but neuronal survival is not enhanced by chronic hyperosmolar conditions.

Neural Activity Protects Hypothalamic Magnocellular Neurons against Axotomy-Induced Programmed Cell Death

“…The slightly greater cell death found in the VP MCNs in our experiments may be attributable to the more proximal site of the injury. The greater vulnerability of the VP MCNs versus the OT MCNs to the axotomy-induced cell death in our experiments (Table 1) is in agreement with other reports in which different modes of axonal injury were used (Herman et al, 1987;Dohanics et al, 1992Dohanics et al, , 1996Alonso et al, 1996). In addition, we observed the expected polydipsia and polyuria in the ME lesioned rats (data not shown), typical of the diabetes insipidus found after injuries to the neurohypophysial axons (O'Connor, 1952;Moll, 1962;Dellmann, 1973;Raisman, 1973;Dellmann et al, 1988).…”

“…The results showed that the compression alone produced an 83% decrease in VP MCNs and a 32% decrease in OT MCNs in the SON compared with the unlesioned control rat SONs (Table 1). The extent of this MCN cell death found in the SON after axonal compression in the ME is comparable with the 65% decrease in VP MCNs and a 31% decrease in OT MCNs in the SON found by Dohanics et al (1996) after compressing the neurohypohysial stalk. The slightly greater cell death found in the VP MCNs in our experiments may be attributable to the more proximal site of the injury.…”

“…Figure 1 illustrates the approach that was used to produce axonal damage at the level of the ME by compression and to simultaneously superfuse the SON unilaterally with TTX for 2 weeks in vivo. We used ME compression (Dohanics et al, 1992(Dohanics et al, , 1996 to cause axonal injury, because hypophysectomy or neurolobectomy, which use parapharyngeal approaches, are intrinsically more traumatic procedures. Other procedures such as ME or pituitary stalk transaction can lead to damage of the portal circulation and thereby compromise the blood supply to the anterior lobe and possibly produce hemorrhage at the base of the skull .…”

“…Previous studies in vivo using experimental treatments that are inferred to reduce excitatory input to the HNS (Herman et al, 1986(Herman et al, , 1987Dohanics et al, 1996) found that this produced a substantial decrease in MCN survival after HNS axon injury. The reverse treatment, chronic hypernatremia, did not alter the survival of the axotomized MCNs in one study (Dohanics et al, 1996); however, in another study that used a chronic intermittent saltloading paradigm, there was an increase in the survival of MCN cells (Huang and Dellmann, 1996). In view of these reports, we tested the hypothesis that after axotomy, neural activity was neuroprotective in the HNS by directly inhibiting both electrical and synaptic activity unilaterally in the SON by local superfusion of TTX (Ludwig et al, 1995) in vivo.…”

“…Chronic hyponatremia, which inhibits secretory activity in the MCNs (Verbalis et al, 1986;Robinson et al, 1990;Verbalis and Dohanics, 1991), also produces an enhanced degeneration of the MCNs after axonal injury in the HNS (Dohanics et al, 1996). Because both of these treatments lead to decreased functional activity of the MCNs, it was suggested that there is a neuroprotective role of functional activity in the HNS after axonal injury (Herman et al, 1987;Dohanics et al, 1996). The latter view is also consistent with the findings of Huang and Dellmann (1996), who showed that chronic intermittent salt loading, which increases the functional activity of the MCNs in the HNS, produced an increased survival of the VP MCNs after hypothalamic stalk transection.…”