| In vivo: |
| Neuromolecular Med. 2014 Jun;16(2):350-9. | | Attenuation of reserpine-induced pain/depression dyad by gentiopicroside through downregulation of GluN2B receptors in the amygdala of mice.[Pubmed: 24584520 ] | Epidemiological studies demonstrate that pain frequently occurs comorbid with depression. Gentiopicroside (Gent) is a secoiridoid compound isolated from Gentiana lutea that exhibits analgesic properties and inhibits the expression of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the anterior cingulate cortex of mice. However, the effects of Gent on the Reserpine-induced pain/depression dyad and its underlying mechanisms are unclear.
METHODS AND RESULTS:
Reserpine administration (1 mg/kg subcutaneous daily for 3 days) caused a significant decrease in the nociceptive threshold as evidenced by the reduced paw withdrawal latency in response to a radiant heat source and mechanical allodynia. Behavioral detection indicated a significant increase in immobility time during a forced swim test, as well as decreased time in the central area and total travel distance in an open field test. Furthermore, reserpinized animals exhibited increased oxidative stress. Systemic Gent administration dose-dependently ameliorated the behavioral deficits associated with Reserpine-induced pain/depression dyad. At the same time, the decrease in biogenic amine levels (norepinephrine, dopamine, and serotonin) was integrated with the increase in caspase-3 levels and GluN2B-containing NMDA receptors in the amygdala of the Reserpine-injected mice. Gent significantly reversed the changes in the levels of biogenic amines, caspase-3, and GluN2B-containing NMDA receptors in amygdala. However, Gent did not affect the expression of GluN2A-containing NMDA receptors. The inhibitory effects of Gent on oxidative stress were occluded by simultaneous treatment of GluN2B receptors antagonist Ro25-6981.
CONCLUSIONS:
Our study provides strong evidence that Gent inhibits Reserpine-induced pain/depression dyad by downregulating GluN2B receptors in the amygdala. | | Behav Brain Res. 2013 Sep 15;253:68-77. | | Cognitive, motor and tyrosine hydroxylase temporal impairment in a model of parkinsonism induced by reserpine.[Pubmed: 23831411] | Studies have suggested that cognitive deficits can precede motor alterations in Parkinson's disease (PD). However, in general, classic animal models are based on severe motor impairment after one single administration of neurotoxins, and thereby do not express the progressive nature of the pathology.
METHODS AND RESULTS:
A previous study showed that the repeated administration with a low dose (0.1mg/kg) of the monoamine depleting agent Reserpine induces a gradual appearance of motor signs of pharmacological parkinsonism in rats. Here, we showed this repeated treatment with Reserpine induced a memory impairment (evaluated by the novel object recognition task) before the gradual appearance of the motor signs. Additionally, these alterations were accompanied by decreased tyrosine hydroxylase (TH) striatal levels and reduced number of TH cells in substantia nigra pars compacta (SNpc). After 30 days without treatment, Reserpine-treated animals showed normal levels of striatal TH, partial recovery of TH cells in SNpc, recovery of motor function, but not reversal of the memory impairment. Furthermore, the motor alterations were statistically correlated with decreased TH levels (GD, CA1, PFC and DS) and number of TH cells (SNpc and VTA) in the brain.
CONCLUSIONS:
Thus, we extended previous results showing that the gradual appearance of motor impairment induced by repeated treatment with a low dose of Reserpine is preceded by short-term memory impairment, as well as accompanied by neurochemical alterations compatible with the pathology of PD. | | Exp Gerontol. 2009 Jun-Jul;44(6-7):462-6. | | Reserpine ameliorates Abeta toxicity in the Alzheimer's disease model in Caenorhabditis elegans.[Pubmed: 19264117 ] |
METHODS AND RESULTS:
Earlier we have reported that Reserpine, an antihypertensive drug, known to downregulate biogenic amines through inhibition of the vesicular monoamine transporter (VMAT), increases longevity of Caenorhabditis elegans with a high quality of life, namely, enhanced and prolonged mobility (Srivastava et al., 2008). As neurodegenerative diseases are of adult onset, we addressed the protective ability of Reserpine against neurodegenerative diseases, especially Alzheimer's disease (AD). In the well established AD model in C. elegans, Amyloid beta (Abeta) is expressed in the muscles and Abeta toxicity is manifested as paralysis (Link, 1995).
CONCLUSIONS:
In this model, Reserpine significantly delayed paralysis and increased the longevity. In addition, Reserpine provided thermotolerance, but interestingly the Abeta transcript and expression levels remains grossly unchanged. |
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