Astrocytes: biology and pathology

Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions

Respiratory properties of blood in flatback turtles (Natator depressus)

Oxygen equilibrium curves and other respiratory-related variables were determined on blood from the flatback turtle (Natator depressus) and, for comparison, on some samples from the loggerhead turtle (Caretta caretta). The oxygen carrying capacity of the flatback turtle, 4.9-8.7 mmol l(-1) (n = 49), is at the high end of the range in diving reptiles. Oxygen affinity (P-50) was similar in both species at 5% CO2, ranging from 37 to 55 mmHg (43 mmHg +/- 5.3 SD, n = 24, 25 degrees C, pH 7.17) in flatbacks and 43-49 mmHg in loggerheads (46 mmHg +/- 2.0 SD, n = 7, 25 degrees C, pH 7.13), whereas at 2% CO2, flatbacks had a higher oxygen affinity. The curves differed in sigmoidicity, with Hill n coefficients of 2.8 and 1.9 in flatbacks and loggerheads, respectively. The Bohr effect was small in both the species, consistent with results from other sea turtles. Lactate levels were high, perhaps because the samples were taken from turtles coming ashore to lay eggs. Flatbacks are rarely found in waters deeper than 45 m. It is suggested that they have a respiratory physiology particularly suited to sustain prolonged shallow dives

Physiological and immunocytochemical evidence that glutamatergic neurotransmission is involved in the activation of arm autotomy in the featherstar Antedon mediterranea (Echinodermata: Crinoidea)

The crinoid echinoderm Antedon mediterranea autotomises its arms at specialised skeletal joints known as syzygies that occur at regular intervals along the length of each arm. Detachment is achieved through the nervously mediated destabilisation of ligament fibres at a particular syzygy. The aim of this investigation was to identify neurotransmitters that are involved in the autotomy response. Physiological experiments were conducted on isolated preparations of syzygial joints, which can be induced to undergo autotomy-like fracture by applying stimulatory agents such as elevated [K+]o. Initial experiments with elevated [K+]o showed that the autotomy threshold (the minimum amount of stimulation required to provoke autotomy) is lowest in syzygies at the arm base and rises distally. Of a range of neurotransmitter agonists tested, only L-glutamate invoked syzygial destabilisation, as did its analogues L-aspartate, -amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainate, but not L-(+)-2-amino-4-phosphonobutyrate (L-AP4) or N-methyl-D-aspartate (NMDA). The implication that L-glutamate stimulates syzygial fracture through AMPA/kainate-like receptors was supported by the finding that the action of L-glutamate was inhibited by the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Acetylcholine depressed the response of syzygial preparations to L-glutamate, suggesting a possible mechanism by which the autotomy threshold could be varied constitutively and facultatively. An immunocytochemical method employing a polyclonal antibody against L-glutamate conjugated to glutaraldehyde revealed L-glutamate-like immunoreactivity in all components of the putative neural pathway controlling the autotomy reflex, including the epidermis, brachial nerve, syzygial nerves and cellular elements close to the syzygial ligaments. We conclude that it is highly probable that L-glutamate acts as an excitatory neurotransmitter in the activation of arm autotomy in A. mediterranea