Ciliary neurotrophic factor increases the survival of magnocellular vasopressin and oxytocin neurons in rat supraoptic nucleus in organotypic cultures†

Rusnak, Milan; House, Shirley B.; Arima, Hiroshi; Gainer, Harold

doi:10.1002/jemt.10015

Cited by 26 publications

(45 citation statements)

References 37 publications

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“…These immunoreactive neurons are similar in their morphological appearances to MCNs found in the SON in vivo (Armstrong, 1995). Although the MCN phenotypes are present in these cultures, it has also been shown that there is substantial programmed cell death of the MCN cell population in these slices (Vutskits et al, 1998;Rusnak et al, 2002Rusnak et al, , 2003. This is presumably because of the extensive axotomy that these neurons undergo during preparation of the slices.…”

Section: The In Vitro Modelsupporting

confidence: 60%

“…Consistent with the "neurotrophic hypothesis," which posits that the survival of neurons depends on the continuous retrograde supply of trophic factors from target organs (Purves, 1988;Oppenheim, 1989Oppenheim, , 1991, Vutskits et al (1998) proposed that the programmed cell death of MCNs in the HNS is attributable to the loss of specific trophic actors, presumably CNTF, from the neurohypophysis. In this regard, the rescue of the MCNs in vitro by CNTF (Vutskits et al, 1998;Rusnak et al, 2002Rusnak et al, , 2003 and the reversal of the TTX effect (Fig. 8) provide support for this proposal.…”

Section: Discussionmentioning

confidence: 59%

“…In the process of preparing these cultures, coronal cuts are made through the hypothalamus that transect all of the MCN axons projecting to the neurohypophysis. This is essentially equivalent to ME transection and neurohypophysectomy in vivo and produces substantial retrograde degeneration of the MCNs both in the SON and in the PVN in vitro (Vutskits et al, 1998;Rusnak et al, 2002Rusnak et al, , 2003. That this degeneration of the MCNs in vitro is attributable primarily to the axotomy and not to a general excitotoxicity caused by the damage to slice preparation is suggested by findings that the MCNs are relatively resistant to glutamate excitotoxicity and ischemia (Curras-Collazo et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Organotypic hypothalamic cultures were made as described previously (House et al, 1998;Rusnak et al, 2002). Briefly, 6-d-old Sprague Dawley pups (Taconic) were decapitated, and their brains were quickly removed.…”

Section: Methodsmentioning

confidence: 99%

“…This is presumably because of the extensive axotomy that these neurons undergo during preparation of the slices. Previous studies have focused on the ability of the neurotrophic factor CNTF to counter this cell death in vitro (Vutskits et al, 1998;Rusnak et al, 2002Rusnak et al, , 2003.…”

Section: The In Vitro Modelmentioning

confidence: 99%

See 4 more Smart Citations

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

Shahar¹,

House²,

Gainer³

2004

J. Neurosci.

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Axotomy typically leads to retrograde neuronal degeneration in the CNS. Studies in the hypothalamo-neurohypophysial system (HNS) have suggested that neural activity is supportive of magnocellular neuronal (MCN) survival after axotomy. In this study, we directly test this hypothesis by inhibiting neural activity in the HNS, both in vivo and in vitro, by the use of tetrodotoxin (TTX). After median eminence compression to produce axonal injury, unilateral superfusion of 3 M TTX into the rat supraoptic nucleus (SON), delivered with the use of a miniature osmotic pump for 2 weeks in vivo, produced a decrease in the number of surviving MCNs in the TTX-treated SON, compared with the contralateral untreated side of the SON. In vitro application of 2.5 M TTX for 2 weeks to the SON in organotypic culture produced a 73% decrease in the surviving MCNs, compared with untreated control cultures. Raising the extracellular KCl in the culture medium to 25 mM rescued the MCNs from the axotomy-and TTX-induced cell death. These data support the proposal that after axotomy, neural activity is neuroprotective in the HNS.

show abstract

Section: The In Vitro Modelsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: The In Vitro Modelmentioning

confidence: 99%

See 3 more Smart Citations

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

Shahar¹,

House²,

Gainer³

2004

J. Neurosci.

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Absence of axonal sprouting following unilateral lesion in 125‐day‐old rat supraoptic nucleus may be due to age‐dependent decrease in protein levels of ciliary neurotrophic factor receptor alpha

Askvig

Watt

2019

J of Comparative Neurology

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Within the supraoptic nucleus (SON) of a 35‐day‐old rat, we previously demonstrated a collateral sprouting response that reinnervates the partially denervated neural lobe (NL) after unilateral lesion of the hypothalamo‐neurohypophysial tract. Others have shown a decreased propensity for axonal sprouting in an aged brain; therefore, to see if the SON exhibits a decreased propensity for axonal sprouting as the animal ages, we performed a unilateral lesion in the 125‐day‐old rat SON. Ultrastructural analysis of axon profiles in the NL of the 125‐day‐old rat demonstrated an absence of axonal sprouting following injury. We previously demonstrated that ciliary neurotrophic factor (CNTF) promotes process outgrowth from injured magnocellular neuron axons in vitro. Thus, we hypothesized that the lack of axonal sprouting in the 125‐day‐old rat SON may be due to a reduction in CNTF or the CNTF receptor components. To this point, we found that as the rat ages there is significantly less CNTF receptor alpha (CNTFRα) protein in the uninjured, 125‐day‐old rat compared to the uninjured, 35‐day‐old rat. We also observed that protein levels of CNTF and the CNTF receptor components were increased in the SON and NL following injury in the 35‐day‐old rat, but there was no difference in the protein levels in the 125‐day‐old rat. Altogether, the results presented herein demonstrate that the plasticity within the SON is highly dependent on the age of the rat, and that a decrease in CNTFRα protein levels in the 125‐day‐old rat may contribute to the loss of axonal sprouting following axotomy.

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In vitro functionality of isolated embryonic hypothalamic vasopressinergic and oxytocinergic neurons: modulatory effects of brain-derived neurotrophic factor and angiotensin II

Moreno

Piermaria

Gaillard

et al. 2010

Endocr

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There are only a few studies on the ontogeny and differentiation process of the hypothalamic supraoptic-paraventriculo-neurohypophysial neurosecretory system. In vitro neuron survival improves if cells are of embryonic origin; however, surviving hypothalamic neurons in culture were found to express small and minimal amounts of arginine-vasopressin (AVP) and oxytocin (OT), respectively. The aim of this study was to develop a primary neuronal culture design applicable to the study of magnocellular hypothalamic system functionality. For this purpose, a primary neuronal culture was set up after mechanical dissociation of sterile hypothalamic blocks from 17-day-old Sprague-Dawley rat embryos (E17) of both sexes. Isolated hypothalamic cells were cultured with supplemented (B27)-NeuroBasal medium containing an agent inhibiting non-neuron cell proliferation. The neurosecretory process was characterized by detecting AVP and OT secreted into the medium on different days of culture. Data indicate that spontaneous AVP and OT release occurred in a culture day-dependent fashion, being maximal on day 13 for AVP, and on day 10 for OT. Interestingly, brain-derived neurotrophic factor (BDNF) and Angiotensin II (A II) were able to positively modulate neuropeptide output. Furthermore, on day 17 of culture, non-specific (high-KCl) and specific (Angiotensin II) stimuli were able to significantly (P < 0.05) enhance the secretion of both neuropeptides over respective baselines. This study suggests that our experimental design is useful for the study of AVP- and OT-ergic neuron functionality and that BDNF and A II are positive modulators of embryonic hypothalamic cell development.

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Ciliary neurotrophic factor increases the survival of magnocellular vasopressin and oxytocin neurons in rat supraoptic nucleus in organotypic cultures†

Cited by 26 publications

References 37 publications

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

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

Absence of axonal sprouting following unilateral lesion in 125‐day‐old rat supraoptic nucleus may be due to age‐dependent decrease in protein levels of ciliary neurotrophic factor receptor alpha

In vitro functionality of isolated embryonic hypothalamic vasopressinergic and oxytocinergic neurons: modulatory effects of brain-derived neurotrophic factor and angiotensin II

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