Astroglial Regulation of Magnocellular Neuroendocrine Cell Activities in the Supraoptic Nucleus

Abstract

Studies on the interactions between astrocytes and neurons in the hypothalamo-neurohypophysial system have significantly facilitated our understanding of the regulation of neural activities. This has been exemplified in the interactions between astrocytes and magnocellular neuroendocrine cells (MNCs) in the supraoptic nucleus (SON), specifically during osmotic stimulation and lactation. In response to changes in neurochemical environment in the SON, astrocytic morphology and functions change significantly, which further modulates MNC activity and the secretion of vasopressin and oxytocin. In osmotic regulation, short-term dehydration or water overload causes transient retraction or expansion of astrocytic processes, which increases or decreases the activity of SON neurons, respectively. Prolonged osmotic stimulation causes adaptive change in astrocytic plasticity in the SON, which allows osmosensory neurons to reserve osmosensitivity at new levels. During lactation, changes in neurochemical environment cause retraction of astrocytic processes around oxytocin neurons, which increases MNC's ability to secrete oxytocin. During suckling by a baby/pup, astrocytic processes in the mother/dams exhibit alternative retraction and expansion around oxytocin neurons, which mirrors intermittently synchronized activation of oxytocin neurons and the post-excitation inhibition, respectively. The morphological and functional plasticities of astrocytes depend on a series of cellular events involving glial fibrillary acidic protein, aquaporin 4, volume regulated anion channels, transporters and other astrocytic functional molecules. This review further explores mechanisms underlying astroglial regulation of the neuroendocrine neuronal activities in acute processes based on the knowledge from studies on the SON.

Keywords: Glial fibrillary acidic protein; Lactation; Morphological plasticity; Osmolality; Oxytocin; Vasopressin.

Figure 1.

Drawing of anatomical features of the hypothalamo-neurohypophysial system. A and B. Sketches of the system in coronal (A) and sagittal (B) projections. The red-colored and green-colored areas in A indicate vasopressin and oxytocin neurons-rich areas, respectively. The blue-colored area and lines in the SON show astrocytic somata and processes, respectively. Abbreviations: 3^rd V, the third cerebral ventricle; A. Pit, anterior pituitary; ME, median eminence; mPVN, magnocellular division of the PVN; OC, optic chiasm; Pit, pituitary, P.Pit, posterior pituitary; pPVN, parvocellular division of the PVN; SON, supraoptic nucleus.

Figure 2.

Diagram of cellular interactions between magnocellular neuroendocrine cells with other cellular components in the supraoptic nucleus (SON). A. Ionotropic receptors and their agonists and co-agonists with D-serine shuttling. B. Volume-regulating machineries. C. Synaptic connections and tripartite synapses. D. Neurovascular units in the supraoptic nucleus and at the posterior pituitary. E. Glial plasmalemmal neurochemical transporters and their regulation by β-alanine. F. Feedback loop between MNCs and astrocytes by the mediation of OT/VP and ATP. G. Gap junctional communication and cellular apposition. Abbreviations: AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; AQP4, aquaporin 4; GABA_AR, GABA_A receptor; GAT, GABA transporter; GFAP, glial fibrillary acidic protein; GLUT, glutamate transporter; Glut. terminal, glutamatergic terminal; NMDAR, N-methyl-D-aspartate receptor; OT, oxytocin; VP, vasopressin; VRAC, volume-regulated anion channel.

Figure 3.

Diagram of the cellular interactions between astrocytes and MNCs underlying different states of astrocytic morphological plasticity in the SON. A. Resting condition. B. Retraction of astrocytic processes and GFAP filaments. C. Expansion of GFAP filaments and astrocytic processes. Annotations refer to Figure 2.

Figure 4.

Diagram of the hypothetic mechanisms underlying GFAP-associated astrocytic plasticity in the SON. A-C. Interaction of GFAP with F-actin, membrane anchor proteins, actin linker proteins, volume-regulating proteins and signaling molecules under different states of astrocytic plasticity. A. Resting condition. B. Retraction of GFAP filaments in astrocytic processes. C. GFAP expansion in the processes. Abbreviations: AQP4, aquaporin 4; DP, dystrophin; F-actin, filamentous actin; glial fibrillary acidic protein; pERK1/2, phosphorylated extracellular signal-regulated kinase 1/2; PKA, protein kinase A; VRAC, volume-regulated anion channel.