Joseph L. Cheatwood

Infusion of GAT1-saporin into the medial septum/vertical limb of the diagonal band disrupts self-movement cue processing and spares mnemonic function.

Degeneration of the septohippocampal system is associated with the progression of Dementia of the Alzheimer’s type (DAT). Impairments in mnemonic function and spatial orientation become more severe as DAT progresses. Although evidence supports a role for cholinergic function in these impairments, relatively few studies have examined the contribution of the septohippocampal GABAergic component to mnemonic function or spatial orientation. The current study uses the rat food-hoarding paradigm and water maze tasks to characterize the mnemonic and spatial impairments associated with infusing GAT1-Saporin into the medial septum/vertical limb of the diagonal band (MS/VDB). Although infusion of GAT1-Saporin significantly reduced parvalbumin-positive cells in the MS/VDB, no reductions in markers of cholinergic function were observed in the hippocampus. In general, performance was spared during spatial tasks that provided access to environmental cues. In contrast, GAT1-Saporin rats did not accurately carry the food pellet to the refuge during the dark probe. These observations are consistent with infusion of GAT1-Saporin into the MS/VDB resulting in spared mnemonic function and use of environmental cues; however, self-movement cue processing was compromised. This interpretation is consistent with a growing literature demonstrating a role for the septohippocampal system in self-movement cue processing.

Stearidonic Acid: Is There a Role in the Prevention and Management of Type 2 Diabetes Mellitus?

Obesity and its related comorbidities are major public health concerns in the United States with over two-thirds of adults and one-third of children classified as overweight or obese. The prevalence of type 2 diabetes mellitus (T2DM) has similarly risen to an estimated 25.8 million, which accounts for a staggering

Soy protein diet increases skilled forelimb reaching function after stroke in rats.

174 billion in annual healthcare costs. Identification of dietary interventions that protect against the development of T2DM would markedly reduce the medical and economic consequences of the disease. Hence, we review current evidence supporting a role of (n-3) PUFA in T2DM and explore potential therapeutic implications of stearidonic acid (SDA). The low consumption of fish in the US along with a reduced efficiency to interconvert most plant (n-3) PUFA highlights a need to find alternative sources of (n-3) PUFA. The efficient biological conversion of SDA to EPA underscores the potential implications of SDA as a source of (n-3) PUFA. The full therapeutic efficacy of SDA remains to be further determined. However, recent data have suggested a protective role of SDA consumption on markers of dyslipidemia and inflammation. The AHA recommends that healthy individuals consume oily fish at least twice per week and individuals with a history of cardiovascular disease consume 1 g of EPA+DHA/d. These goals will likely not be met by the typical American diet. Therefore, SDA may represent a sustainable alternative to marine-based (n-3) PUFA and may have novel therapeutic efficacy regarding the development of T2DM.

Cholinergic deafferentation of the hippocampus causes non-temporally graded retrograde amnesia in an odor discrimination task

Stroke is a leading cause of lasting disability. Dietary strategies aimed at increasing post-stroke outcomes are lifestyle alterations which could be easily implemented by people at risk of occlusive stroke. Soy diets have been demonstrated to provide some benefits in the short term following stroke, but longer time periods have not been studied. Further, carefully defined diets containing soy protein isolates have not been investigated. In the current study, male Long Evans Hooded rats were fed semi-purified diets containing either sodium caseinate or soy protein isolate. Rats were trained to perform the skilled forelimb reaching task and subsequently underwent unilateral middle cerebral artery occlusion (MCAO) to induce a stroke lesion. After stroke, rats remained on the same diet and were tested daily for a period of 8 weeks to observe their performance on the skilled forelimb reaching task. In the first week following stroke, rats receiving the soy protein-containing diet (SP) demonstrated less severe reaching deficits than rats fed the Na caseinate-containing diet (CAS) (p<0.05). These results suggest that a soy protein-based diet provides significant protection from neurological damage following MCAO stroke in rats.

The medial frontal cortex contributes to but does not organize rat exploratory behavior.

Dementia of the Alzheimers type (DAT) is a neurodegenerative disorder marked by loss of hippocampal cholinergic tone and significant memory impairments, specifically for memories acquired prior to disease onset. The nature of this relationship, however, remains debated. The current study used the string pulling task to evaluate the temporal effects of odor discrimination learning in animals with selective cholinergic lesions to determine the role of the septohippocampal cholinergic system in mnemonic function. Rats with 192-IgG-Saporin lesions to the medial septum had a higher number of correct responses in the reversal training when compared to sham rats, suggesting an inability to retrieve the previously learned discrimination; however, no temporal gradient was observed. Furthermore, there were no group differences when learning a novel odor discrimination, demonstrating the ability for all rats to form new memories. These results establish a role for the cholinergic medial septum projections in long-term memory retrieval. The current study provides a behavioral assessment technique to investigate factors that influence mnemonic deficits associated with rodent models of DAT.

Unilateral forelimb sensorimotor cortex devascularization disrupts the topographic and kinematic characteristics of hand movements while string-pulling for food in the rat

Animals use multiple strategies to maintain spatial orientation. Dead reckoning is a form of spatial navigation that depends on self-movement cue processing. During dead reckoning, the generation of self-movement cues from a starting position to an animals current position allow for the estimation of direction and distance to the position movement originated. A network of brain structures has been implicated in dead reckoning. Recent work has provided evidence that the medial frontal cortex may contribute to dead reckoning in this network of brain structures. The current study investigated the organization of rat exploratory behavior subsequent to medial frontal cortex aspiration lesions under light and dark conditions. Disruptions in exploratory behavior associated with medial frontal lesions were consistent with impaired motor coordination, response inhibition, or egocentric reference frame. These processes are necessary for spatial orientation; however, they are not sufficient for self-movement cue processing. Therefore it is possible that the medial frontal cortex provides processing resources that support dead reckoning in other brain structures but does not of itself compute the kinematic details of dead reckoning.

Unilateral lesions of the dorsocentral striatum (DCS) disrupt spatial and temporal characteristics of food protection behavior.

&NA; String‐pulling by the rat is a bimanual act, in which an upright animal retrieves a piece of food attached to the end of the string by downward hand‐over‐hand movements. The present study compared the movements of string‐pulling, using topographic and kinematic measures of hand movement, in control rats and rats with unilateral sensorimotor motor cortex lesion produced by removal of the pia matter. In the first week following devascularization, the rhythmicity and accuracy of string‐pulling movements decomposed; however, thereafter the rhythm of bilateral alternation was restored. Over 70 days of testing, distance traveled decreased for both hands in the control and lesion groups, suggesting that both groups displayed an increase in string‐pulling efficiency. Nevertheless, the lesion group exhibited more missed string contacts with the (contralateral‐to‐lesion) hand and more grasps in which the string was hooked between the digits with both hands. In addition, an increase in mouth grasps was observed in the lesion group. Motion capture analyses revealed that the lesion group exhibited longer reach and withdraw movements and these movements were longer for the ipsilateral‐to‐lesion vs contralateral‐to‐lesion hand. Thus, although rhythmicity of string‐pulling behavior recovers after sensorimotor cortex devascularization, the contralateral‐to‐lesion hand contributed less to string pulling and requires mouth grasps to stabilize the string for grasping. The results are discussed in relation to contemporary theories of the contributions of the forelimb motor cortex to skilled movement and the potential use of string‐pulling as a therapy for brain injury. HighlightsString pulling is a highly organized manipulatory scale movement.Sensorimotor cortex devascularization produces persistent disruptions this organization.The pattern of disruptions is consistent with impaired direction and distance estimation.

Diet, Stroke, and Traumatic Brain Injury

Spatial and temporal information processing provide a foundation for higher cognitive functions. The survival of animals depends on integrating spatial and temporal information to organize behavior. In general, previous research has focused on only one source of information processing; however, there is evidence to support a convergence in the processing of egocentric-spatial and temporal information within a cortico-striatal system of structures. The current study evaluated the contributions of the dorsocentral striatum (DCS) to egocentric-spatial and temporal (within the seconds-to-minutes range) processing of information using a food protection task. Long-Evans rats received unilateral NMDA lesions of the DCS followed by testing in a food protection task. Performance in this task is mediated by the motivation of the animal to consume a food item, their perception of the time required to consume a food item, their sensory ability to process egocentric cues, and their motor ability to evade an incoming conspecific. Unilateral DCS lesions were shown to impact both spatial and temporal characteristics of food protection. These results suggest that the DCS may be a critical structure for the integration of egocentric-spatial and temporal information within the interval timing range.

Stearidonic Acid: Is There a Role in the Prevention and Management of Type 2

Abstract Stroke and traumatic brain injury (TBI) affect many people each year, and no effective therapies have been approved for use after the damage is done. Interestingly, foods eaten by stroke or TBI patients may have the ability to reduce neurological damage and even enhance recovery. Herein, we cover the current state of the research into finding new dietary routes to reduce the impact of stroke and TBI. Research into the benefits of diets that contain compounds from sources such as soy, fish, ginseng, tea, and others may soon lead to exciting new therapies to benefit patients.