Decrease In Spontaneous Motor Activity Research Articles

Amelioration of Brain Damage after Treatment with the Methanolic Extract of Glycyrrhizae Radix et Rhizoma in Mice.

Glycyrrhizae Radix et Rhizoma (GR) is a traditional herbal medicine widely used in Asian countries. GR was the most frequently used medicine among stroke patients in Donguibogam, the most representative book in Korean medicine. In the present study, we investigated the neuroprotective effects of the GR methanolic extract (GRex) on an ischemic stroke mice model. Ischemic stroke was induced by a 90 min transient middle cerebral artery occlusion (MCAO), and GRex was administered to mice with oral gavage after reperfusion of MCA blood flow. The MCAO-induced edema and infarction volume was measured, and behavioral changes were evaluated by a novel object recognition test (NORT). Immunofluorescence stains and Western blotting identified underlying mechanisms of the protective effects of GRex. GRex post-treatment in mice with MCAO showed potent effects in reducing cerebral edema and infarction at 125 mg/kg but no effects when the dosage was much lower or higher than 125 mg/kg. GRex inhibited the decrease of spontaneous motor activity and novel object recognition functions. The neuroprotective effects of GRex on ischemic stroke were due to its regulation of inflammation-related neuronal cells, such as microglia and astrocytes.

CNS Disorders: Treatment Approach with Novel Derivatives of Coumarins in Experimental Albino Mice

Aim : The present study was aimed to assess the treatment of CNS disorders of the novel coumarin (Benzopyran-2-one) derivatives i.e., 2- (4-isobutylphenyl) -N- (4-methyl-2-oxo-2H-chromen-7-yl) propanamide (comp-I), 2-(2-(2,6- dichlorophenylamino) phenyl) –N- (4- methyl-2-oxo-2H-chromen-7-yl) acetamide (comp-II) and 2-(1-(4-chlorobenzoyl)-6-methoxy-2-methyl-1H-indol-3-yl)-N-(4-methyl-2-oxo-2H-chromen-7-yl) acetamide (comp-III) by using the various pharmacological activities i.e., anti-convulsant, anxiolytic, spontaneous motor activity, skeletal muscle relaxant and analgesic activities along with assay of serum gamma amino butyric acid (GABA) levels. Methods: Investigation of all CNS Disorders were evaluated by performing the various pharmacological activities using the different screening models i.e., anti-convulsant activity by pentylenetetrazole (PTZ) induced seizure model, anxiolytic activity (exploratory behaviour) by evasion test, assay of GABA levels after anti-convulsant model was performed by using chromatographic technique, spontaneous motor activity (SMA) by actophotometer test, skeletal muscle relaxation by rotarod test and analgesic activity by Eddy’s hot plate and Haffner’s tail clip methods in Wistar albino mice. Results: All the Coumarin derivatives showed significant anti-convulsant activity by prolonging the onset of seizures and reducing the duration of seizures and mortality rate when compared with control group. The test compounds showed significant anxiolytic effect. The serum GABA levels were significantly elevated in the treated groups, when compared with that of control group. The test compounds showed significant decrease in the spontaneous motor activity. The test compounds significantly showed a skeletal muscle relaxation after 30 min of dosing. The test compounds showed significant increase in paw licking time to heat stimuli in hot plate method and increase in the reaction time of mice to dislodge the clip. Conclusion: The present study has revealed that all the Benzopyran-2-one derivatives possess significant neuropharmacological properties confirmed by anti-convulsant, anxiolytic, skeletal muscle relaxant, analgesic effects and decrease in spontaneous motor activity at a dose of 20 mg/kg p.o. in swiss albino mice.

Short-Term Exposure to Enriched Environment in Adult Rats Restores MK-801-Induced Cognitive Deficits and GABAergic Interneuron Immunoreactivity Loss.

Perinatal injections of N-methyl-D-aspartate (NMDA) receptor antagonist in rodents emulate some cognitive impairments and neurochemical alterations, such as decreased GABAergic (gamma aminobutyric acid) interneuron immunoreactivity, also found in schizophrenia. These features are pervasive, and developing neuroprotective or neurorestorative strategies is of special interest. In this work, we aimed to investigate if a short exposure to enriched environment (EE) in early adulthood (P55-P73) was an effective strategy to improve cognitive dysfunction and to restore interneuron expression in medial prefrontal cortex (mPFC) and hippocampus (HPC). For that purpose, we administered MK-801 intraperitoneally to Long Evans rats from postnatal days 10 to 20. Twenty-four hours after the last injection, MK-801 produced a transient decrease in spontaneous motor activity and exploration, but those abnormalities were absent at P24 and P55. The open field test on P73 manifested that EE reduced anxiety-like behavior. In addition, MK-801-treated rats showed cognitive impairment in novel object recognition test that was reversed by EE. We quantified different interneuron populations based on their calcium-binding protein expression (parvalbumin, calretinin, and calbindin), glutamic acid decarboxylase 67, and neuronal nuclei-positive cells by means of unbiased stereology and found that EE enhanced interneuron immunoreactivity up to normal values in MK-801-treated rats. Our results demonstrate that a timely intervention with EE is a powerful tool to reverse long-lasting changes in cognition and neurochemical markers of interneurons in an animal model of schizophrenia.

Characterization of dystrophin deficient rats: a new model for Duchenne muscular dystrophy.

A few animal models of Duchenne muscular dystrophy (DMD) are available, large ones such as pigs or dogs being expensive and difficult to handle. Mdx (X-linked muscular dystrophy) mice only partially mimic the human disease, with limited chronic muscular lesions and muscle weakness. Their small size also imposes limitations on analyses. A rat model could represent a useful alternative since rats are small animals but 10 times bigger than mice and could better reflect the lesions and functional abnormalities observed in DMD patients. Two lines of Dmd mutated-rats (Dmdmdx) were generated using TALENs targeting exon 23. Muscles of animals of both lines showed undetectable levels of dystrophin by western blot and less than 5% of dystrophin positive fibers by immunohistochemistry. At 3 months, limb and diaphragm muscles from Dmdmdx rats displayed severe necrosis and regeneration. At 7 months, these muscles also showed severe fibrosis and some adipose tissue infiltration. Dmdmdx rats showed significant reduction in muscle strength and a decrease in spontaneous motor activity. Furthermore, heart morphology was indicative of dilated cardiomyopathy associated histologically with necrotic and fibrotic changes. Echocardiography showed significant concentric remodeling and alteration of diastolic function. In conclusion, Dmdmdx rats represent a new faithful small animal model of DMD.

Bromocriptine Effect in Spontaneous Motor Activity Using Albino Mice

Bromocriptine is a potent agonist at the D2 receptor. The aim of this study is to investigate the bromocriptine effect in spontaneous motor activity, using variable doses with acute and subacute administration and variable onset of measurement using albino mice. Acute intraperitonealadministration of bromocriptine using doses of 0.625, 2.5, 5, and 10mg/kg and thecontrol group administration of 1% tween 80(n=7) were used. Spontaneous motor activity was scored after 30 and 60min of administration. Subacute administration is as follows:group1was administered 1% tween 80asa control and group2 was administered 10mg/kg bromocriptine. Spontaneous motor activity was scored using an open field test. Acute administration of bromocriptine after 30min (0.625 and 2.5mg/kg) did not show any significant changes in spontaneous motor activity while 5 and 10mg/kg produced a significant decrease. Acute administration of bromocriptine after 60min produced a significant decrease in spontaneous motor activity, with 0.625, 2.5, 5, and 10mg/kgdoses. Subacute administration of bromocriptine significantly increased spontaneous motor activity,compared to control. It is concluded that acute administration of bromocriptine at 30min decreased spontaneous motor activity, only with higher doses while its acute administration after 60min decreased spontaneous motor activity,with all doses (0.625, 2.5, 5, and 10mg/kg). As subacute administration increased spontaneous motor activity,these findings conclude that bromocriptine which produced its effect in spontaneous motor activityis time and dose dependence.

General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug for xerostomia in Sjögren's syndrome. 1st communication: effects on general behavior and central nervous system.

A novel muscarinic receptor agonist, SNI-2011 ((+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate, cevimeline, CAS 153504-70-2), is a candidate therapeutic drug for xerostomia in Sjögren's syndrome. The general pharmacological properties of this drug on general behavior and the central nervous system were investigated in mice, rats and cats. 1. General behavior: When SNI-2011 was administered orally to mice at 100 mg/kg, mydriasis, a decrease of spontaneous motor activity, tremor, convulsions, salivation, abnormal posture, abnormal gait, reduced grip strength and reduced response against external stimulating were observed, and 2 out of 6 animals died. At 10 mg/kg or lower, no particular sign was observed except mydriasis, which appeared to be caused via the peripheral muscarinic acetylcholine receptors. 2. Central nervous system: SNI-2011 had no effect on the motor coordination in mice. Hypothermia was observed in rats and reduced spontaneous motor activity, analgesia and enhanced maximum electroshock-induced convulsions were observed in mice after oral administration of 30 mg/kg SNI-2011. Slight increase in the rate of theta-wave band in the hippocampal EEG of rats and spinal multisynaptic reflexes in cats were observed after intravenous injection of 10 mg/kg SNI-2011. At an oral dose of 10 mg/kg, prolongation of thiopental-induced sleeping time in mice was observed. The prolongation of sleeping time was inhibited by a peripheral muscarinic antagonist. These results suggest that SNI-2011 has muscarinic effects on general behavior and the central nervous system at the doses approximately 10-fold higher than the effective doses needed for saliva secretion.

Inhibition of fatty acid oxidation activates transforming growth factor-beta in cerebrospinal fluid and decreases spontaneous motor activity

We have previously reported that transforming growth factor (TGF)-beta in the cerebrospinal fluid (CSF) is involved in the mechanism underlying the regulation of spontaneous motor activity (SMA) by the central nervous system after exercise. However, it remained unclear what physiological condition triggers the activation of TGF-beta. We hypothesized that the shortage of energy derived from fatty acid (FA) oxidation observed in the early phase of exercise activated TGF-beta in the CSF. To test this hypothesis, we investigated whether mercaptoacetate (MA), an inhibitor of FA oxidation, could induce an activation of TGF-beta in the CSF and a decrease in SMA. Intraperitoneal (i.p.) administration of MA activated TGF-beta in CSF in rats and depressed SMA; 2-deoxyglucose, an inhibitor of carbohydrate oxidation, on the other hand, depressed SMA but failed to activate CSF TGF-beta. Intracisternal administration of anti-TGF-beta antibody abolished the depressive effect of MA on SMA. We also found that the depression of SMA and the activation of TGF-beta in the CSF by i.p. MA administration were eliminated by vagotomy. Our data suggest that TGF-beta in the CSF is activated by the inhibition of FA oxidation via the vagus nerve and that this subsequently induces depression of SMA.

Fumigation of rabbit warrens with chloropicrin produces poor welfare outcomes - a review

Chloropicrin (CLPN) is used in Australia and New Zealand as a warren fumigant for the control of exotic European rabbits (Oryctolagus cuniculus) but is no longer registered for this purpose in the United States or the European Union. This review summarises the mammalian toxicology and clinical records from 56 accounts where signs, symptoms and pathology have been related to a range of CLPN concentrations. The approach follows a general principle where an assessment of the humaneness of vertebrate pest control techniques should be firstly based upon a thorough synopsis of published behavioural, physiological and pathological impacts. Chloropicrin produces intense irritation by stimulation of trigeminal nerves and brief exposures to concentrations of ≤1 ppm can severely irritate the eyes and cause lacrimation in mammals. Beyond 8 ppm, exposures are reported to be painful and incapacitating in humans. Mammals experience an array of common signs and symptoms including: headache, nausea, diarrhoea, laboured breathing, decrease in spontaneous motor activity, salivation, rhinorrhea, blood stains around the nose and mouth, painful irritation of mucous membranes, profuse lacrimation, audible obstruction of respiration and distress vocalisation. Acute pathological changes from CLPN exposure can cause death in mammals from pulmonary oedema, bronchopneumonia, emphysema or general destructive changes and necrosis of the small and medium bronchi. Overall, the signs, symptoms and pathology arising from CLPN exposure at any airborne concentration beyond 0.3 ppm indicate that it must be assumed to cause suffering in all mammals. Exposure to CLPN that is not acutely lethal may debilitate rabbits and other species and cause a protracted death over hours or days. To produce a humane death a fumigant must be non-irritating, have an initial depressive action on the central nervous system and/or produce a rapid death without protracted distress while having little ability to cause debilitation or chronic injury. Given that CLPN has none of these characteristics, it cannot be considered to be acceptably humane.

Neuromuscular changes in a rat model of colitis

Intracolonic administration of Trichinella spiralis larvae in rats causes colitis with features similar to ulcerative colitis, notably with inflammation predominantly limited to the colonic mucosa. Our aim was to characterize the functional and neurochemical changes occurring within the myenteric (MP) and submucosal plexuses (SMP) during T. spiralis-induced colitis. Infected rats had decreased body weight, altered stool consistency and elevated myeloperoxidase activity, 6 and 14 days post-infection (PI). Responses to acetylcholine and KCl in circular muscle strips were reduced in infected tissues, demonstrating an impairment of contractility. In addition, there was a decrease in spontaneous motor activity and reduced sensitivity to the nitric oxide synthase (NOS) inhibitor L-NOArg, corresponding with a significant reduction in NOS immunoreactive neurons in the MP of infected animals. T. spiralis did not alter the total number of myenteric or submucosal neurons. Substance P innervation of submucosal blood vessels was reduced after infection, as were submucosal calretinin and calbindin immunoreactive neurons. No changes in choline acetyltransferase and calcitonin gene-related peptide immunoreactivity were observed. T. spiralis-induced colitis causes profound neuromuscular adaptations. The reduction in NOS neurons appears to underlie changes in motility.

Increase in transforming growth factor-β in the brain during infection is related to fever, not depression of spontaneous motor activity

When viral infection occurs, this information is transmitted to the brain, and symptoms such as fever and tiredness are induced. One of the causes of these symptoms is the secretion of proinflammatory cytokines in blood and the brain. In this study, the i.p. administration of polyinosinic:polycytidylic acid (poly I:C), a synthetic double-stranded RNA, to rats was used as an infection model. Poly I:C decreased spontaneous motor activity (SMA) 2 h after i.p. administration, and this decrease was maintained thereafter. The concentration of active transforming growth factor-β (TGF-β) in cerebrospinal fluid (CSF) increased 1 h after the administration. This increase occurred earlier than those in the concentrations of other proinflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), in serum. The intracisternal administration of an anti-TGF-β antibody partially inhibited fever induced by poly I:C administration; however, this treatment did not affect the decrease in SMA. Furthermore, intracisternal administration of TGF-β raised the body temperature. These results indicate that TGF-β in the brain, which was increased by poly I:C administration, is associated with fever but not with a decrease in SMA.

Pharmacological Evaluation of the Central Nervous System Activity of Aframomum melegueta Seed Extract in Mice

Objective: To study the effects of intraperitoneal injection of aqueous seed extract of Aframomum melegueta (AM) on the central nervous system (CNS) in mice. Materials and methods: The study sought to evaluate the effects of the extract on the general behaviour of the animals (Irwin test), on pentobarbitone-induced sleeping time, on methamphetamine-induced stereotyped behaviour, on motor coordination, and on convulsive seizures induced by isoniazid and picrotoxin. AM was tested at a dose range of 5-400 mg/kg. Results: AM (50-200 mg/kg) produced a significant decrease in spontaneous motor activity and also caused a dose-related prolongation of pentobarbital-induced sleeping time. At a dose range of 100-400 mg/kg, a significant inhibition of methamphetamine (35 mg/kg, i. p) induced stereotyped behaviour was observed. Furthermore, it offered a significant protection against convulsions induced by isoniazid (200 mg/kg, i.p). However, it failed to modify the convulsive action of picrotoxin (10 mg/kg, i.p) and did not cause any significant effect in the motor coordination of animals on the rota-rod machine. Conclusion: The results of this study suggest that A. melegueta seed extract possesses central nervous system depressant activity.

Analgesic and behavioral effects of amphetamine enantiomers, p-methoxyamphetamine and n-alkyl- p-methoxyamphetamine derivatives

The analgesic effects of (+)- and (−)-amphetamine (AMPH), (±)- p-methoxyamphetamine (MA), (±)- N-methyl- p-methoxyamphetamine (MMA) and (±)- N-ethyl- p-methoxyamphetamine (EMA) were compared using two different algesimetric tests in rats. In the formalin test, (+)-AMPH elicited significant antinociception at doses of 0.2, 2 and 8 mg/kg (i.p.); (−)-AMPH was active at 2 and 8 mg/kg, but not at 0.2 mg/kg; MA elicited very potent and long-lasting antinociception; MMA was less active than MA; EMA showed significant effects only at doses of 2 and 8 mg/kg. In the C-fiber evoked nociceptive reflex assay, i.v. (+)- and (−)-AMPH were ineffective, but the methoxy derivatives showed a similar pattern of action combining inhibitory and excitatory actions. To clarify apparent discrepancies between both algesimetric tests, some behavioral motor performance tests were carried out. These tests confirm the motor stimulatory properties of (+)-AMPH, not shared by the methoxylated amphetamine derivatives. The three methoxy derivatives elicited some stereotypies related to dopaminergic activation such as grooming behavior. (+)-AMPH was also the only drug to increase the acquisition of CARs while MA and EMA were without effect. Avoidance conditioning was seriously impaired in rats injected with MMA. This conditioned behavior can be related to the significant decrease of spontaneous motor activity observed with this drug. In conclusion, the introduction of a para-methoxy group strongly increases the analgesic effects of amphetamine without its stimulatory behavioral effects. The introduction of N-alkyl substituents decreases the analgesic potency of MA.

Does prenatal stress affect the motoric development of rat pups?

Pregnant rats were exposed to an acute or a repeated stress (presence of a cat) either at the 10th or the 14th gestational day, and the development of their offspring was studied during the first 2 weeks of life. Motor development was measured by different tests: rooting reflex, vibrissae placing response, righting reflex, negative geotaxis. Other landmarks such as eye opening and spontaneous locomotor activity were also recorded. The results showed that, except for the rooting reflex which was most often enhanced (while not significantly) in prenatally stressed rats, the development of the vibrissae placing response, the righting reflex and the negative geotaxis behavior was delayed in the offspring of dams stressed at the 10th gestational day and not (or almost not) in the offspring of dams stressed at the 14th gestational day, the delay being more severe when the prenatal stress was repeated than when it was acutely administered. The spontaneous motor activity was also altered in repeatedly prenatally stressed rats, whatever the day of pregnancy when it was administered, while it was unaffected in acutely prenatally stressed animals. The delay in motor reflexes development was interpreted as alterations in maturation of nervous structures sustaining motor skills, while permanent decrease of spontaneous motor activity was explained by emotional and motivational alterations due to prenatal stress.

GHB differentially affects morphine actions on motor activity and social behaviours in male mice

There are several reports suggesting that gamma-hydroxybutyric acid (GHB) influences the endogenous opioid system. The present study aimed to investigate the effects of GHB on motor and social activities and to examine its influence on morphine's actions on these behaviours. In a first experiment, several doses of GHB were studied but only the highest (200 and 400 mg/kg) produced a decrease in spontaneous motor activity measured in an actimeter cage. When hyperactivity induced by injecting 50 mg/kg of morphine was evaluated, all the GHB doses efficiently counteracted this morphine action. Using the paradigm of isolation-induced aggression, administration of 200 mg/kg of GHB significantly decreased threat and attack without impairing motor activity and, in addition, increased time spent in social contact. GHB increased morphine's suppression of threat or nonsocial exploratory behaviours. In conclusion, the interaction between GHB and the opioid systems was confirmed, with the drug having an additive effect on morphine-affected social behaviours but counteracting morphine-induced increases in motor activity.

Neuropharmacological Effects of Hibiscus sabdariffa Aqueous Extract

The neuropharmacological effects of the aqueous extract of Hibiscus sabdariffa (HS) calyx were studied in rodents. HS (100, 200 and 400 mg/kg, i.p.) caused a remarkable dose-dependent decrease in spontaneous motor activity in mice and increased the duration of pentobarbital (40 mg/kg, i.p.) induced sleep in rats. The extract (100-400 mg/kg, i.p.) significantly reduced the exploratory behaviour in mice. The extract significantly inhibited the intensity of apomorphine (1 mg/kg, s.c.) induced stereotypic behaviour and attenuated climbing in the mice dose-dependently. Similarly, chlorpromazine (3 mg/kg, i.p.) blocked apomorphine induced stereotype behaviour significantly. The intraperitoneal LD 50 of the extract was estimated to be greater than 5000 mg/kg. These results suggest that the aqueous extract of HS may contain psychoactive substances that are sedative in nature and which contribute to its use in traditional medicine as sedative.

Antiaggressive and motor effects of the DA release inhibitor CGS 10746B

In the present study the effects of a wide range of doses of the dopamine release inhibitor CGS 10746B were evaluated in spontaneous activity and in aggressive behaviour using the paradigm of isolation-induced aggression. The two higher doses (8 and 16 mg/kg) produced a decrease in spontaneous motor activity. Antiaggressive effects were observed after administration of doses from 4 mg/kg upwards. At this dose, CGS 10746B diminished threat and attack, and although an increase in immobility was observed, no impairment of other motor behaviours was presented. With higher doses, aggression was practically abolished but with a concomitant effect on many other behaviours. When animals were separated depending on their latency of attack, those that showed a long attack latency (LAL) presented a stronger response to 4 mg/kg than those that had a short attack latency (SAL), which were not affected in their aggression by this dose. We can conclude that presynaptic dopamine function is necessary for the normal expression of aggressive behaviours, since CGS 10746B reduces aggression at doses that do not affect spontaneous motor activity. Aggr. Behav. 27:382–390, 2001. © 2001 Wiley-Liss, Inc.

Antiaggressive and motor effects of the DA release inhibitor CGS 10746B

AbstractIn the present study the effects of a wide range of doses of the dopamine release inhibitor CGS 10746B were evaluated in spontaneous activity and in aggressive behaviour using the paradigm of isolation‐induced aggression. The two higher doses (8 and 16 mg/kg) produced a decrease in spontaneous motor activity. Antiaggressive effects were observed after administration of doses from 4 mg/kg upwards. At this dose, CGS 10746B diminished threat and attack, and although an increase in immobility was observed, no impairment of other motor behaviours was presented. With higher doses, aggression was practically abolished but with a concomitant effect on many other behaviours. When animals were separated depending on their latency of attack, those that showed a long attack latency (LAL) presented a stronger response to 4 mg/kg than those that had a short attack latency (SAL), which were not affected in their aggression by this dose. We can conclude that presynaptic dopamine function is necessary for the normal expression of aggressive behaviours, since CGS 10746B reduces aggression at doses that do not affect spontaneous motor activity. Aggr. Behav. 27:382–390, 2001. © 2001 Wiley‐Liss, Inc.

N-type calcium channel blockers — tools for modulation of cerebral functional units?

According to in vitro and in vivo studies, the direct application of N-type calcium channel blockers as for instance ω-conotoxin GVIA (ω-ctx) potently inhibits the release of neurotransmitters like dopamine. To find out whether this effect could be used for modulation of neurological functions, ω-ctx was used for continuous infusion into the functionally well characterized rat striatum. Over the 2-week time course of intrastriatal application, rats developed a decrease in spontaneous motor activity, spontaneous rotational asymmetry towards the side of application, and behavioral supersensitivity to apomorphine. After the end of infusion period, all functional deficits showed reversibility. The pattern of spontaneous neurological deficits - in particular supersensitivity to apomorphine - points to a substantial unilateral alteration of dopaminergic transmission due to ω-ctx, which is suggested also by an increase in dopamine receptor protein expression within the ipsilateral striatum. Time course and reversibility of neurological deficits caused by ω-ctx, as well as a lack of dopamine depletion contrast findings after selective destruction of dopaminergic neurons and support a functional modulation of dopaminergic transmission. The present study suggests that ω-ctx is an effective potent tool for the unilateral and reversible intracerebral modulation of neuronal circuits. Intracerebral application of ω-ctx could possibly open the way to therapeutic interventions.

Does long-term physical exercise counteract age-related Purkinje cell loss? A stereological study of rat cerebellum

Physical exercise affects properties of the central nervous system that may increase the brain's ability to counteract degenerative changes. We have previously reported that rats trained from 5 to 23 months of age have less age-related decrease in spontaneous motor activity than sham-treated sedentary rats. Each rat ran at a speed of 20 m/min on a horizontal treadmill, for 20 minutes, two times per day, 5 days a week. In the present study we have carried out stereological analyses of the cerebella of the same rats. The total number of Purkinje cells was estimated with the optical fractionator technique, the local volumes of individual Purkinje cells with the planar rotator technique, and the volumes of the cerebellar layers with Cavalierìs principle. We found that sedentary aged rats have 11% fewer Purkinje cells and 9% smaller Purkinje cell soma volumes (both 2P = 0.02) than exercised aged rats, and that exercised aged rats have the same number of Purkinje cells as young rats. These findings indicate that the degree of age-associated degenerative changes in parts of the central nervous system is dependent on earlier life style and health habits and may be prevented or delayed by physical exercise.

Transforming growth factor-beta activated during exercise in brain depresses spontaneous motor activity of animals. Relevance to central fatigue

Intracerebroventricular administration into sedentary mice of the high molecular mass fraction of cerebrospinal fluid (CSF) from exercise-exhausted rats produced a decrease in spontaneous motor activity [K. Inoue, H. Yamazaki, Y. Manabe, C. Fukuda, T. Fushiki, Release of a substance that suppresses spontaneous motor activity in the brain by physical exercise, Physiol. Behav. 64 (1998) 185–190]. CSF from sedentary rats had no such effect. This suggests the presence of a substance regulating the urge for motion as a response to fatigue. A bioassay system using hydra, a freshwater coelenterate, showed an activity indistinguishable from transforming growth factor-beta (TGF-β) in the CSF from exercise-fatigued rats, while not in that from sedentary rats. The increase in the concentration of active TGF-β in the CSF from exercise-fatigued rat was also ascertained by another bioassay system using mink lung epithelial cells (Mv1Lu). Injection of TGF-β into the brains of sedentary mice elicited a similar decrease in spontaneous motor activity in a dose-dependent manner. Increasing the exercise load on rats raised both the levels of active TGF-β and the activity of depression on spontaneous motor activity of mice in the CSF of rats. Taken together, these results suggest that exercise increases active TGF-β in the brain and it creates the feeling of fatigue and thus suppresses spontaneous motor activity.