Neuropeptide expression in rat dorsal root ganglion cells and spinal cord after peripheral nerve injury with special reference to galanin

Villar, Marcelo J.; Cortés, Roser; Theodorsson, Elvar; Wiesenfeld‐Hallin, Zsuzsanna; Schalling, Martin; Fahrenkrug, Jan; Emson, Piers C.; Hökfelt, Tomas

doi:10.1016/0306-4522(89)90411-9

Cited by 439 publications

(198 citation statements)

References 89 publications

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“…To accomplish these diverse biological functions, GAL gene expression is highly plastic. GAL is dramatically up-regulated in rat anterior pituitary by estrogen (Kaplan et al, 1988), in the rat basal forebrain by nerve growth factor (Planas et al, 1997) and following experimental injury to the rat central and peripheral nervous systems, including olfactory bulbectomy (Holmes and Crawley, 1996), hypophysectomy (Villar et al, 1994), neurochemical dorsal raphe lesions (Gabriel et al, 1995), immunotoxic basal forebrain lesions (Hartonian et al, 2002), potassium chloride (KCl)-mediated cortical spreading depression (Shen et al, 2003), and sciatic nerve transection (Villar et al, 1989).…”

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confidence: 99%

Ectopic galanin expression and normal galanin receptor 2 and galanin receptor 3 mRNA levels in the forebrain of galanin transgenic mice

Counts

Pérez

et al. 2005

Neuroscience

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Abstract-The functional interactions of the neuropeptide galanin (GAL) occur through its binding to three G proteincoupled receptor subtypes: galanin receptor (GALR) 1, GALR2 and GALR3. Previously, we demonstrated that GALR1 mRNA expression was increased in the CA1 region of the hippocampus and discrete hypothalamic nuclei in galanin transgenic (GAL-tg) mice. This observation suggested a compensatory adjustment in cognate receptors in the face of chronic GAL exposure. To evaluate the molecular alterations to GALR2 and GALR3 in the forebrain of GAL overexpressing mice, we performed complementary quantitative, real-time PCR (qPCR), in situ hybridization, and immunohistochemistry in select forebrain regions of GAL-tg mice to characterize the neuronal distribution and magnitude of GAL mRNA and peptide expression and the consequences of genetically manipulating the neuropeptide GAL on the expression of GALR2 and GALR3 receptors. We found that GAL-tg mice displayed dramatic increases in GAL mRNA and peptide in the frontal cortex, posterior cortex, hippocampus, septal diagonal band complex, amygdala, piriform cortex, and olfactory bulb. Moreover, there was evidence for ectopic neuronal GAL expression in forebrain limbic regions that mediate cognitive and affective behaviors, including the piriform and entorhinal cortex and amygdala. Interestingly, regional qPCR analysis failed to reveal any changes in GALR2 or GALR3 expression in the GAL-tg mice, suggesting that, contrary to GALR1, these receptor genes are not under ligand-mediated regulatory control. The GAL-tg mouse model may provide a useful tool for the investigation of GAL ligand-receptor relationships and their role in normal cognitive and affective functions as well as in the onset of neurological disease.

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confidence: 99%

Ectopic galanin expression and normal galanin receptor 2 and galanin receptor 3 mRNA levels in the forebrain of galanin transgenic mice

Counts

Pérez

et al. 2005

Neuroscience

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“…Similarly, axotomy also up-regulates galanin expression in motor (4) and sympathetic (5) neurons. The rise in expression in the dorsal horn after axotomy is modest compared with the marked elevation in the DRG (6), reflecting an increase in anterograde transport of galanin from the cell body to the site of injury (7), analogous to that described in axotomized sympathetic neurons (8). Despite these findings, there is no direct evidence that galanin plays a role in axonal regeneration after injury.…”

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Targeted disruption of the galanin gene reduces the number of sensory neurons and their regenerative capacity

Holmes

Mahoney²,

King³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

193

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The neuropeptide galanin is expressed developmentally in the dorsal root ganglion (DRG) and is rapidly up-regulated 120-fold after peripheral nerve section in the adult. Here we report that adult mice carrying a loss-of-function mutation in the galanin gene have a 13% reduction in the number of cells in the DRG associated with a 24% decrease in the percentage of neurons that express substance P. These deficits are associated with a 2.8-and 2.6-fold increase in the number of apoptotic cells in the DRG at postnatal days 3 and 4, respectively. After crush injury to the sciatic nerve, the rate of peripheral nerve regeneration is reduced by 35% with associated long-term functional deficits. Cultured DRG neurons from adult mutant mice demonstrate similar deficits in neurite number and length. These results identify a critical role for galanin in the development and regeneration of sensory neurons. D amage to a peripheral nerve causes changes within the cell body that promote neuronal survival, axonal regeneration, and functional recovery. Under favorable conditions, for instance after a crush injury, most nerve fibers successfully regenerate. However, in many clinically relevant circumstances, traumatic or disease-induced nerve injury has a poor outcome with only limited return of function and often with considerable delay. The molecular and cellular interactions that control the degree and rate of peripheral nerve regeneration are poorly understood and remain important clinical and scientific issues.In an attempt to define the mechanisms that regulate neuronal survival and regeneration, we and others have used the approach of studying factors whose expression patterns are known to change in response to injury. One of the most potent changes in the dorsal root ganglion (DRG) after peripheral nerve injury is the 120-fold increase in the levels of the 29-aa neuropeptide galanin (1). Studies have demonstrated that galanin is expressed at high levels in most cells of the developing DRG from day 16 of gestation until shortly after birth (2). In the adult, galanin is expressed at low levels in only 2-3% of DRG cells, which are predominantly small fiber neurons (1). After axotomy, mRNA and peptide are abundantly expressed in 40-50% of all DRG neurons (3) and remain elevated while the nerve is regenerating (1). Similarly, axotomy also up-regulates galanin expression in motor (4) and sympathetic (5) neurons. The rise in expression in the dorsal horn after axotomy is modest compared with the marked elevation in the DRG (6), reflecting an increase in anterograde transport of galanin from the cell body to the site of injury (7), analogous to that described in axotomized sympathetic neurons (8). Despite these findings, there is no direct evidence that galanin plays a role in axonal regeneration after injury.We previously have generated mice carrying a loss-of-function mutation in the galanin gene (9) and most recently have demonstrated that the chronic absence of galanin throughout prenatal and postnatal development causes an atte...

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“…Substance P and calcitonin gene-related peptide are downregulated whereas vasoactive intestinal peptide and galanin are upregulated (15)(16)(17)(18)(19)(20). We have recently demonstrated that the vasoactive intestinal peptide level is increased in the same sensory neurons that previously produced substance P (21) and that vasoactive intestinal peptide took over the role of tachykinins as excitatory mediators of nociceptive input (22).…”

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confidence: 99%

Galanin-mediated control of pain: enhanced role after nerve injury.

Wiesenfeld‐Hallin

Langel

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

181

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The endogenous inhibitory role of the neuropeptide galanin in pain transmission and spinal cord excitability was demonstrated by the use of a high-affinity galanin receptor antagonist, M-35 [galanin-(1-13)-bradykinin-(2-9)-amide]. M-35, which displaced 12'I-labeled galanin from membranes of rat dorsal spinal cord with an IC50 of 0.3 nM, dose-dependently antagonized the effect of intrathecal galanin on the flexor reflex. M-35 potentiated the facilitation of the flexor reflex by conditioning stimulation of cutaneous unmyelinated afferents in rats with intact nerves and the potentiating effect of M-35 on the conditioning-stimulation-induced reflex facilitation of the cutaneous unmyelinated afferents was strongly enhanced after axotomy. These results demonstrate that endogenous galanin plays a tonic inhibitory role in the mediation of spinal cord excitability, and it is particularly noteworthy that this function of galanin is remarkably enhanced after peripheral nerve section.The neuropeptide galanin (1) consists of 29 amino acids, has been shown to occur in a relatively small population of dorsal root ganglion cells and spinal cord interneurons (2-4), and may be involved in sensory modulation. Although some reports indicated that intrathecal (i.t.) galanin has a hyperalgesic effect and i.t. galanin antibody produces analgesia (5), overwhelming evidence suggests that galanin primarily has an inhibitory effect in sensory transmission at the spinal level. Thus, i.t. galanin blocks the facilitatory effect of the flexor reflex produced by the conditioning stimulation (CS) of unmyelinated afferents and by i.t. applied excitatory neuropeptides, such as substance P and calcitonin gene-related peptide (6-8). Galanin also selectively depresses spinal nociceptive reflexes in adult and newborn rats with no or very limited effect on the monosynaptic reflex (6, 9, 10). Galanin (i.t.) has been reported to cause analgesia without motor deficits (11) and iontophresis ofgalanin hyperpolarizes dorsal horn neurons (12). Galanin also inhibits the peripheral consequences of antidromic activation of cutaneous unmyelinated (C) afferents, such as the plasma extravasation, mediated by the release of substance P (13,14).Peripheral axotomy has dramatic effects on peptidergic sensory afferents. Substance P and calcitonin gene-related peptide are downregulated whereas vasoactive intestinal peptide and galanin are upregulated (15)(16)(17)(18)(19)(20). We have recently demonstrated that the vasoactive intestinal peptide level is increased in the same sensory neurons that previously produced substance P (21) and that vasoactive intestinal peptide took over the role of tachykinins as excitatory mediators of nociceptive input (22). We have also shown that the depressive effect of galanin on the flexor reflex is enhanced after nerve section (23) and it antagonized the excitatory effect of vasoactive intestinal peptide, with which it coexists in axotomized sensory neurons (7). Based on these findings, we have hypothesized that one role for upr...

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Neuropeptide expression in rat dorsal root ganglion cells and spinal cord after peripheral nerve injury with special reference to galanin

Cited by 439 publications

References 89 publications

Ectopic galanin expression and normal galanin receptor 2 and galanin receptor 3 mRNA levels in the forebrain of galanin transgenic mice

Ectopic galanin expression and normal galanin receptor 2 and galanin receptor 3 mRNA levels in the forebrain of galanin transgenic mice

Targeted disruption of the galanin gene reduces the number of sensory neurons and their regenerative capacity

Galanin-mediated control of pain: enhanced role after nerve injury.

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